dev2011 exam list
Dorsal rami
**
Primordial germ cell journey (in mouse)
- About 6 cells in mouse embryo are specified - These cells proliferate - Subset express Stella, now commited to gerline - PGCs migrate to gonads (passive and active) - Extensive proliferation - PGCs colonise the gonads and undergo sex determination
3 major approaches to the study of dev bio
- Anatomical - Experimental - Genetic
Describe how apoptosis sculpts tissues e.g. in lumen
- Cells undergo apoptosis to form the lumen - Epithelial cells become polarised around the lumen - Begin to form junctional complexes and microvilli present at the apical membrane
Describe Metaphase (3)
- Chromosomes align at the equatorial plane - Spindle fibres attached to chromosomes - Independent assortment occurs
Explain how somitogenesis in humans work
- Day 25 - 3-4 somites form per day - 42-44 somite pairs are formed along the neural tube, position from the cranial region of the embryo
Key techniques of experimental embryology? (2 things)
- Defect experiment - Transplantation experiment
Paraxial mesoderm elongation occurs how? and in what direction?
- Elongation of it in the cranial-caudal directions occurs with the extension of the notochord
List the types of adult stem cells present in the body and provide an example of an adult stem cell therapy
- Epidermal SCs - Intestinal SCs - Blood - hematopoietic SCs - Sperm An adult stem cell therapy would be: - Bone marrow transplantation - Epidermal skin repair
Describe necrosis
- Induced by tissue injury 🡪 Cells swell and burst releasing their intracellular contents 🡪 Can lead to death as phagocytes don't receive the chemical signals to engulf the dead cells
Genetic hierarchy
- Pattern-forming genes - Master genes that specify cell lineages - Genes that regulate cell phenotype - Genes that code for tissue-specific functional products
Mitochondria function
- cellular metabolism e.g. kreb cycle - cell differentiation, apoptosis - passed down maternally only - 2nd location of DNA in cell
What are the 4 different intercellular signalling
- contact - dependent paracrine synaptic endocrine
Give examples of ciliopathies
- craniofacial abnormalities - incomplete bilateral syndactyly
Defects in mitochondrial function
- exercise intolerance - LHON - acute vision loss one one eye
Describe the proliferative phase
- highly regulated by estrogen. prefominantly, the division of stromal cells, and epithelial cells that make up glandular and luminal epithelium of fnctional layer of endo
What are the 3 types of cartilage?
- hyaline (e.g. end of bones) - fibrous (e.g. in bone-ligament joints) - elastic (e.g. ear, epiglottis, auditory tubes)
Describe sirenomelia (caudal dysgenesis)
- insufficient mesoderm is formed in the caudal-most region (tail end) of the embro - issues with lower limbs, fused
Disadvantages of Drosophila
- invertebrates - lack blood vessels - don't generate antibodies to fight disease (so not useful for immunology)
Generation of vasculature
- migration of endothelial cells from the mesonephros occurs after SRY expression has commenced - vasculature is all outside the cords - sertoli cells provie all the nutrients
Cremaster muscle
- raises testes during sex, or under fear stimulus - skeletal muscle
How long does receptivity last for and at what day does it occur of the menstrual cycle
- receptivity phase lasts for 4 days of the cycle - occurs days 19-23 of menstrual cycle
How would you test if NCC progenitors are really multipotent?
1. Can genetically label individual NCCs. Labels all of the NCC with different fluro markers. 2. Trace what those cells become in vivo.
Migration pathways of NCCs (steps)
1. Following induction, NCC undergo epithelial to mesenchymal transition 2. NCC delaminate from the neural folds and start their migration 3. Migration is determined by intrinsic properties and external environment
Describe some defining properties of stem cells
1. It is not itself terminally differentiated 2. It can divide without limit (animal lifetime) 3. When it divides, each daughter has a choice: it can either remain a stem cell, or it can embark on a course leading to terminal differentiation (asymmetric division)
Epithelial cells apical surface
1. Microvilli 2. Cilia 3. Stereocilia
Describe notochord in patterning
1. Patterning the Neural Tube - Notochord signals the formation of the floor plate, mainly via the Hedgehog pathway 2. Reinforcement and maintenance of events begun during gastrulation - Left-right asymmetry, support in the organisation of cardiac and pancreatic development
Describe placental development
1. Requires trophoblast invasion into maternal decidua 2. Maternal artery remodelling 3. Development of villi & fetal vessels
What is required for placental development?
1. Requres trophoblast invasion into maternal decidua 2. Maternal artery remodelling 3. Development of villi and fetal vessels
Uterus consists of? (5 things)
1.Body 2.Fundus (top) 3.Cervix (neck of the uterus) 4.Uterine cavity 5.Cervical canal
How long are cilia?
10 microns
What % have - profound - severe - mild/none intellectual disability?
10% have profound intellectual disability 70% severe, 20% mild or none
Adipose tissue % in women
20 - 25%
Most common autosomal extra chromosomes
21, 18 and 13
Most common extra chromosomes among live births
21, 18 and 13
Down syndrome (DS) is typically characterised by what chromosomal arrangement?
3 chromosomes (trisomy 2)
How common are developmental disorders?
3-4%
Enhancer
A DNA sequence that recognizes certain transcription factors that can stimulate transcription of nearby genes.
Inheritable Down syndrome
A Robertsonian translocation takes place A fragment of 21 is transferred to a second Chromosome - particularly 14 or 15. Parent has balanced genetic material, so no phenotype. But if the child inherits normal Cr21 and the Cr14 with 21 then it will have Down S despite not having trisomy.
Basophils
A circulating leukocyte that produces histamine.
Robertsonian translocation
A fragment of chromosome 21 is transferred to a second chromosome
Signalling centre
A localised region of the embryo that can influence how surrounding cells will develop
What is blood?
A loose connective tissue Mostly liquid (plasma) with cellular components
Why are we interested signalling?
A lot of birth defects that occur result from or result in signalling defects
Describe 2 ways where normal SC division has failed, resulting in cancer
A lot of tumours have a stromal component - have supporting cells which sends signals to stem cells can reprogram normal cell to become tumour cell by culturing it with niche or cancer cell
Defect experiment
A portion of the embryo is destroyed and the impact on subsequent development is observed
Gene knockout
A reverse genetics approach for studying gene function Patterns of differential gene expression can provide a 'clue' to what tissues genes function in
Lissencephaly
A smooth brain Absence of sulci and gyri
Describe the Polyspermy block
AKA the fast block - Once acrosome reaction occurs, oocyte immediately commences the "fast block" to polyspermy - Egg undergoes massive depolarisation through a Na+ influx - This depolarisation stops any more sperm binding to the egg
Sirenomelia caused by?
Abnormalities in BMP/RA/Wnt/Tsg pathway
Developmental basis on cognitive disorders
Abnormalities in neuronal migration, axon guidance, synaptogenesis
Placenta acreta
Abnormally deep attachment of the placenta Possibly due to a defect in the decidua Can be treated by c-section and hysterectomy
S phase control
Active S cyclin-CDK complexes phosphorylate proteins that make up the pre-replication complexes on DNA replication origins This is to ensure that each pre-replication complex is activated to initiate chromosomal replication and new complexes are prevented from forming
NK cells in development
Activity of NK cells are lower because baby is foregin, don't want to harm it Why pregnant women get more colds, they are a bit immunesuppressed
X laevis
African clawed frog Lives in fresh water
Trabecular Bone
An open network with a honeycomb-like appearance
Hemidesmosome
Anchors cell to basal lamina, using intermediate filaments
Issues with synaptogenesis
Autism spectrum disorder Some affected have a mutation in genes involved in synapse development Includes cell adhesion molecules, structural or regulatory proteins
4) Relapsing polychondritis
Autoimmune-associated cartilage destruction, especially of the nose and ears, causing disfiguration.
3 classes of bone marrow transplants
Autologous Allogenic Umbilical
Sclerotome
Axial skeleton Will form vertebrae and rib cartilage
Why is there lots of innervation in the testis cells?
Bc it is outside and must be protected
Osteocytes
Bone maintenance Derived from osteoblasts
Osteoclasts
Breakdown of bone Derived from HSCs
Problems with neuronal migration
Can cause epilepsy (due to abnormal connections) Also autism
Pericytes
Cells that contribute to new vessel wall
Vacuole
Cellular space for water/other storage
Two types of bone
Compact Trabecular
What is the point of recombination?
Contributes to genetic diversity Although all of your genes are received from your mother and father, they are not the same chromosomes.
Asymmetrical cell division
Daughter cells are different Two types Can occur through intrinsic or extrinsic mechanisms
Differentiation
Development of specialised cell types It is a progressive process that eventually results in a commitment to a certain fate
Pair-rule genes
Divide embryo into units of two segments each If mutated, then deletion in every other segment
What is the role of the lymphatic system?
Drain fluid from tissue and return to cardiovascular system Transport lymphocytes
Loose connective tissue examples
Fat and blood
Endochondral ossification
Formation of bone where cartilage is present
What allows nerves to grow alongside the vessel?
GDNF (glial cell derived nerve growth factor) Blood vessels secrete GDNF
How do notochords development?
Generated from chordamesoderm Chordamesoderm sits immediately beneath the developing CNS It develops a thick etracellular sheath and vacuole - producing osmotic pressure
What happens if you change the target size?
If you remove a limb bud, fewer motor neurons survive. If you add a limb bud, more motor neurons survive
Early diagnosis of developmental abnormalities
In some cases, a diagnosis can allow for surgical treatment of the fetus E.g. cleft palete
Equivalence hypothesis
Individual blastomeres in 2 cell and 4 cell embryos are homogenous
How conserved is somitogenesis?
It is highly conserved It is a precise program of segmentation from cranial to caudal direction Very tightly regulated
Receptivity of the uterine
It is in mid-secretory phase Days 19-23 of the menstrual cycle Stromal cells differentiate, change morphologically where they become rounded and become secretory.
Lamellar bone
Lamellae are thin sheets of calcified bone matrix that are deposited in layers, layers that go perpendicular to each other Lamellar bone make up compact and trabecular, and is highly organised and strong
Name and role of filaments in the nucleus
Lamin Gives structural support, involved in transcriptional regulation and remodelling of the nuclear envelope
Where is embryonic haematopoiesis derived?
Lateral plate mesoderm
Intermediate mesoderm location?
Located between paraxial and lateral mesoderm
Chiasma
Lock together female and male homologues. The chromatids are now glued together, then the arms are then unglued but remain attached at the centromere.
Cell dispersion
Loss of cell-cell adhesion
Delamination
Loss of cell-matrix adhesion
What is SRY
Master transcriptional regulator (gene)
Microtubule treadmilling
Microtubule assembly and disassembly depending on the temperature and surrounding tubulin concentration Addition of subunits at one end (polymerisation), and removal from the other end (depolymerisation)
What deermines axonal length?
Microtubules
Chordamesoderm gives rise to?
Notochord
Main types of glial cells
Oligodendrocytes Astrocytes
Where is VEGF-R1 expressed?
On endothelial cells
Where is VEGF-R2 expressed?
On the haemangioblast
Trabecular bone
Open network with a honeycomb-like appearance
Trophoectoderm
Outside layer of the blastocyst
X laevis reseach advances
Ovarian biology Neurobiology (vertebrate, siplar brain circuitry) Eye and vision research Heart development Immunology Cancer
Gonads
Ovaries and testies
O2 with haemoglobin forms..
Oxyhaemoglobin
Where are somitomeres formed from?
Paraxial mesoderm
Skeletal muscle comes from...
Paraxial mesoderm Forms somites, developments to myotome and becomes skeletal muscle
Placenta previa
Placenta is near he cervix so baby can't be born vaginally
Why is the fetus not rejected by the matneral immune system?
Placental and decidual cells produce factors which modulate maternal immune cell phenotype/subset There are local immune cells like (d)NK, some T helper cells, some macrophages
Progesterone and estrogen
Produced by placenta By end of first trimester, enough is produced to maintain pregnancy in absence of corpus luteum
Lysosome
Produced by the Golgi, contains digestive enzymes that can kill the cell
Asymmetric division type II
Production of a basal or intermediate progenitor cell, which divides at least once prior to differentiation into neurons
Describe a therapeutic application of iPS or ES cells
Production of beta cells for type1 diabetes treatment
Luteal phase hormone
Progesterone It is used in preparation for pregnancy
Which of the following is a function of intermediate filaments?
Provide mechanical support to the cell, and resist tension
Role of amnion
Role: protective buffer against mechanical injury • Surrounds fetus • Liquid-filled • Cavity expands during gestation • Max 1L around 33-34 weeks
Myofibrils
Rows of sacromeres
What happens in Snai1 KO?
SCs are lost from the crypt base
Thermogenic programme and browning of WAT are driven by ?
SNS in response to cold, diet and stress.
Gene important for sex determination
SRY It switches on a cascade of genes responsible for male gonadal development
Three compartments of mature somites
Sclerotome, myotome and dermatome
Components of the basal lamina
Secreted by epithelial cells Has collagen, laminin (glycoprotein), proteoglycan
Decribe internal reproductive anatomy at birth
Sexually dimorphic
Preeclampsia
Shallow trophoblast invasion and artery remodelling results in toxins circulating blood stream
The cytoskeleton is important for
Shape Support Movement
Satellite cells
Small cells that are apposed to muscle fibres within basal lamina It is involved in muscle fibre growth Represents persistent myoblasts, may regenerate damaged muscle fibres by proliferating and fusing
Microcephaly
Small head Can be caused by - insufficient progenitor proliferation - impaired/premature neurogenesis - abnormal increase in cell death in progenitors or neurons
Sarcomere
Smallest contractile unit of skeletal muscle
How good are muscle at regenerating?
Smooth muscle is very good Skeletal and cardiac muscle undergoes terminal differentiation
Difference between cell division in meiosis and mitosis
Somatic cells divide for proliferation Meiosis is for germ cells only, and is a form of reductive division only to form gametes
What determines gender of offspring?
Sperm
Metaphase
Spindles attach to centromeres, chromosomes line up along the mid point between poles
Where do blood cells and endothelium arise?
Splanchnic mesoderm
Lateral Plate mesoderm gives rise to?
Splanchnic, somatic and extraembryonic
How can you regulate RNA processing and translation?
Splicing RNA - (retaining an intron could introduce a stop codon, making a truncated protein) Stability of mRNA
Delamination
Splitting or migration of one sheet into two sheets Requires a loss of adhesion
Angiogenesis
Sprouting of new blood vessels from existing ones
Alcian blue
Stains connective tissues
Eosin
Stains the cytoplasm (pink)
Haematoxylin
Stains the nucleus (blue)
Divisional Assymmetry
Stem Cells have internal assymetry Divides so that daughters receive different determinants
White fat
Stores nutrients, unilocular
Gamma-actin
Stress fibres
What produces CSFs?
Stromal cells - cytokines
Microtubules
Strongest and largest Alpha and beta-tubulin Forms hollow cylinders Form flagella and cilia, centrioles
Microtubules
Strongest and largest component Resist compression Most rigid because of their tubular conformation Composed of alpha- and beta-tubulin that forms a long hollow cylinder (heterodimer)
Glia cells
Supporting cells of the nervous system
What syndrome can occur if sex determination goes wrong? Describe it
Swyer syndrome They have normal 46XY male karyotype but they are: - phenotypically female (external) - streak ovaries - no post-pubertal development of secondary sex characteristics (e.g. boobs, menstruation) - no germ cells
What is the first division in the developing nervous system?
Symmetric
What happens when neurons find their targets?
Synaptopgenesis Making a synapse
Bipotential reproductive system
The indeterminate genital ridge is accompanied by a twin set of ducts and tubes: - Müllerian ducts (ultimately female) - Wolffian ducts (ultimately male)
Where are embyronic stem cells derived from?
The inner cell mass of a blastocyst
Describe the important concept of mesoderm and ectoderm development
The presence and type of mesoderm tissue controls the development of the associated ectoderm
Why is visceral more dangerous the subcutaneous?
The release of visceral fat products directly to the portal circulation and liver may also influence the medical importance
Angiogenesis
The sprouting and extension of new vessels from existing vessels Primary capillary networks are remodelled - making veins and arteries
Dermatome
The subcutaneous tissue and skin
How does a lack of signal trigger apoptosis?
The target tissue produces survival factors Neurotrophin is endocytoses from the axon growth cone, and is transported to the cell body of the neuron It is transported to the cell body back up the axon - retrograde transport
What is the first organ to develop in vertebrate embryos?
The vascular system
Spiral artery
They are spiral to increase the surface area of the blood supply - which is required for pregnancy and menstruation
Shape of osteocytes
They are star shaped They connect to neighbouring osteocytes via cytoplasmic processes
Why are adhesion molecules important in development?
They organise cells into complex tissues and maintain boundaries Therefore changes in cell adhesion result in reorganisation of cells
What is connective tissue?
They support, connect or separate different types of tissues and organs
Mechanisms required for cell communication
To control which signals are emitted and when To enable the signal-receiving cell to interpret the signals
Human blastocyst-uterine interactions
To ensure receptive phase and blastocyst implantation, hormones, cytokines, adhesive molecules and chemokines are secreted or upregulated on cell surface
What does mesenchyme directly give rise to?
To most of the body's connective tissues, from bones and cartilage to the lymphatic and circulatory systems.
Epiphysis
Top part of bone
Cellular differentiation pathway
Totipotent Pluripotent Multipotent Nullipotent
Extracellular signals that can cause apoptosis
Toxins, hormones, growth factors, nitric oxide, heat etc.
What controls DNA translation?
Transcription factors = proteins that bind to DNA and regulate gene transcription Can control their own expression
Reverse genetic approaches
Transgenic Knockout
How is green fluorescent protein (GFP) used?
Transgenic animals can be used to "mark" tissues with Green fluorescent Protein (GFP)
Somites
Transitional embryonic structures, responsible for the segmental organisation of the embryo
Integrins
Transmembrane proteins, they bind to extracellular matrix molecules Link actin cytoskeleton of a cell to various external structures
Which marker is unique to brown fat?
UCP1
Electron microscope
Uses electrons instead of light to detect images - so the resolution is a lot better then a light microscope
How do axons know how to just cross the midline ONCE?
Uses guidance molecules slit and robo (the receptor) Knocking out Slit results in axons not leaving the midline Comm prevents Robo from being expressed at the cell membrane growth cone. But when the axons reaches the midline, increased netrin-frazzled signalling triggers the down regulation of Comm Then Robo is no longer degraded, so Robo is expressed Growth cone responds to Slit repulsion, the axon then stays away from the midline
How can we test whether cells are determined?
We can test whether cells are determined at any particular stage by transplantation experiments.
The final yolk sac
Week 4 of human foetal development, organogenesis is progressing A section of the yolk sac becomes surrounded by endoderm, ultimately incorporated into the embryonic gut Any remaining yolk sac is termed the 'final yolk sac'
Difference between endothelial cells of veins and arteries?
What they express Arteries express the Ephrin-B2 ligand Veins express the receptor, EphB4
Rb
When Rb is inactivated by phosphorylation, genes can now be transcribed to allow the cell to enter S phase
B lymphocytes
When activated, differentiate into plasma cells and produce antibodies
Neuromuscular junction
Where a neuron meets a myocyte, makes it contract
Intercalated discs
Where two cells are attached end to end Found in cardiac muscle only
Examples of signalling pathways that regulate stem cells, but can also drive tumours
Wnt Shh Notch
Functions of blood
X
SRY
a transcription factor encoded on the Y chromosome.
What cell types do we need for development of a testis?
all of them
Selectins
allow cells to adhere to carbohydrates ligands
What is the 4 marker serum test?
alpha fetoprotein, unconjugated oestriol human chorionic gonadotrophin Inhibin A
Counting somites can give you what?
an accurate age of the embryo
Stem cell niche
an area of a tissue that provides a specific microenvironment, in which stem cells are present in an undifferentiated and self-renewable state.
Stem cells can have 2 distinct progeny at division.... what is it?
another stem cell and a more committed cell that can differentiate.
Transcription factors
are the proteins that directly regulate and drive gene expression by interacting with the regulatory region of a gene - its promoter
Which of the following are defining properties of a stem cell? Select all properties that apply. Select one or more: a. Capable of limited cell division b. Daughter cells can self-renew or differentiate c. Terminally differentiated and unipotent d. Undergo cell division without limit
b and d
How do paracrine factors function?
by binding to a receptor that initiates an enzymatic reaction
Which genes on chromosome 21 are associated with Down syndrome? Select one: a. Only genes involved in brain and heart development b. Only the genes whose expression is decreased in Down syndrome c. Only a small proportion, those whose expression is not properly regulated d. All of them are overexpressed and together, cause the changes seen in Down syndrome
c. Only a small proportion, those whose expression is not properly regulated
Define Totipotent and give 1 example
can produce an entire organism e.g. zygote
Cartilage doesnt repair well - why is this the case?
cartilage doesn't repair well because it doesn't have vascularisation
Multipotent
cell with limited potential to develop into many types of differentiated cells
Multipotent
cell with limited potential to develop into many types of differentiated cells Doesn't usually generate cell types from all germ layers e.g. multipotent stem cell
Endothelial cells
cells lining the blood vessels
How is the ectoderm formed?
cells remaining in the epiblast then form the ectoderm
How do endometrial stromal cells prepare for pregnancy?
change morphology (shape) and secretory activity during a process called decidualisation, to form the decidua during pregnancy
Edwards syndrome
chromosome 18 trisomy
Brown adipose tissue
contains cells with multiple lipid droplets interspersed among abundant mitochondria, which give these cells the darker appearance. Both types of adipose tissue have a rich blood supply. energy burning
Vasculogenesis
creation of a blood vessel
Transverse plane
cuts through stomach, or legs, etc.
Endometrium
inner lining of the uterus It is epithelium
Describe the digit pattern in the developing chick limb
is determined by a morphogen gradient - posterior limb bud transplanted to anterior - chick wing is mirrored - explained as the tissue is a signalling centre and secreting morphogen
Homeotic transformation
is when one body segment is transformed into another with different positional identity.
Intermediate mesoderm gives rise to?
kidney and gonads
KO of Tbx5 is expressed in the developing forelimb bud in mice and chicks will cause?
lack of forelimbs
How do the endometrial epithelial cells prepare for pregnancy?
line the lumen of the endometrium and then form the glandular epithelium that reaches down to the basal layer
Euchromatin
loosely packed chromatin
What is microtubule treadmilling?
microtubules assemble and disassemble when heterodimers are added at one end (polymerization) and removed at the other (depolymerisation)
What are the 3 main components of the cytoskeleton?
microtubules, microfilaments/actin filaments, intermediate filaments
Example of dense, regular connective tissue
muscle-tendon junction
Gap genes
organize cells into groups of segments along anterior-posterior axis Mutations result in 'gaps'
Trophoblast
outer cells of the blastocyst that secrete enzymes that allow implantation
Ectoderm
outermost germ layer; produces sense organs, nerves, and outer layer of skin
Therapeutic cloning describes the process where
patient specific ES cell lines could be generated.
Placental previa
placenta grows and covers base of cervix Potential premature detachment late in gestation
How does myometrium prepare for pregnancy?
required for contraction at menses and term delivery
Give examples of a fast response to extracellular signal
seconds to minutes (usually extracellular signals) - Changes in cell movement, secretion and metabolism - Need not involve changes in gene transcription - May involve rapid phosphorylation of effector proteins
What is the cell signalling process?
signalling molecule binding → receptor activation → activation of intracellular signalling proteins → activator of effector proteins
Somitomeres
small bulges in the paraxial mesoderm Will compact into discrete bodies - somites
What is the process called which turns male germ cells into sperm?
spermatogenesis
What is the function of spiral arteries?
spiral arteries needed to increase SA of blood flow to uterine cavity - unique to endometrium
Pampiniform plexus of testicular veins important for?
temperature control
Endoderm
the inner germ layer that develops into the lining of the digestive and respiratory systems
Synapse
the junction between the axon tip of the sending neuron and the dendrite or cell body of the receiving neuron
Most connective tissues are derived from ?
the mesoderm
Mesoderm
the middle layer of an embryo in early development, between the endoderm and ectoderm. Reproductive tract, blood, muscle
White adipose tissue
the more common type, is composed of cells that, when completely developed, contain one large central droplet of whitish-yellow fat in their cytoplasm.
Epigenetics
the study of influences on gene expression that occur without a DNA change
Germinal epithelium
tight junctional connections between the germ cells AND the Sertoli cells
Which cycles occur simultaneously?
uterina and ovarian
Ectopic risk factors
• Endometriosis • Pelvic inflammatory disease • Chlamydia • Smoking • IVF
Lamellae
• Lamellae are thin sheets of calcified bone matrix that are deposited in layers
Main function of WAT
• Specialised for long-term energy storage
How does luminal epithelium become receptive?
• the glandular epithelium becomes highly secretory • the luminal epithelium undergoes considerable changes
What technique obtains samples of foetal cells in the amniotic fluid?
→ Amniocentesis
Measurement of specific growth ratios in the developing foetus?
→ Ultrasound
What technique uses sequencing of particular chromosomes to determine presence of aneuploidy?
"Non-invasive prenatal testing" or "Harmony test" - uses molecular techniques to assess aneuploidy (ie incorrect Chromosomal numbers) - targeted sequencing of autosomal Chromosomes 13, 18, and 21 and X and Y sex Chromosomes to determine normal/abnormal Chromosomal numbers
Heterochromatin
(dark regions) is tightly packed, and is indicative of transcriptionally INACTIVE regions of DNA
Euchromatin
(light regions) is loose, open chromatin, and allows ACTIVE transcription (gene expression)
Ventral rami
**
Oocyte at birth
***
Oocyte in puberty
***
Mesodermal cell fates
*** copy out the diagram
Describe the Acrosome Reaction including what enzymes are involved in the process
- Acrosome contains digestive enzymes including hyaluronidase and acrosin - These enzymes are needed to break through the layer of cumulus cells that surround the egg - Once the cumulus layer is breached, sperm head can reach the egg surface - The acrosome contents then help the sperm head break through the zona pellucida (ZP) proteins on the surface of the egg, allowing the sperm and egg to fuse - The contents of the sperm head (haploid nucleus and centriole) can then enter the egg
What is the cytoskeleton composed of in non dividing ell?
- Actin supporting plasma membrane and span the whole cell - microtubules throughout cytoplasm - intermediate filament support microtubules
Describe commitment
- After proliferation, a subset of the Blimp1 positive cells express Stella, and commit to the germ line
Original Cell Theory components
- All organisms are composed of cells - Cell is the basic unit of life - Cells are produced by the division of pre-existing cells
Describe P53
- Also a negative regulator - Acts to activate the transcription of inhibitors of the cdk/cyclin kinases - Works to block the transition of the cell from G1 to S - If not functional, it cannot stop the cell cycle - More than 50% of tumours contain a mutation or deletion of the p53 gene - Critical in apoptosis
Describe unification
- Apposition and unification of sperm and egg pronuclei after fertilisation - Note: Sperm Centriole ( from the neck of flagellum) duplicates and thus forms the critically important mitotic spindle
Describe specification
- Around 6 cells in the mouse embryo express Blimp1 gene (E5.5-6.5)
Three classes of bone marrow transplants
- Autologous bone marrow transplant (patients own cells) - Allogenic bone marrow transplant (donor stem cells that match) - Umbilical cord blood transplant (stem cells are taken from umbilical cord)
Structure of erythrocytes
- Biconcave disks (SA:V) - Anucleate - Packed with haemoglobin - Flexible so it can cope with small capillaries
Give 3 examples of mammalian stem cell niches
- Bone marrow - Intestinal crypt - Mammary gland
How are BAT organised?
- Brown adipocytes are organized in discrete lobules, surrounded by connective tissue, extensive blood vessels and numerous sympathetic nerves terminating on the adipocytes and blood vessels.
Structure of BAT? and appearance
- Brown adipocytes contain many small lipid inclusions and therefore have a multilocular appearance.
Issues in contact-dependent signalling can cause?
- Cardiac Disease - Cell death during development
Genetic control includes:
- Cell Proliferation - Cell to Cell signalling - Changes in cell shape - Cell Movement - Cell Death - Pattern of gene activity
Developmental processes are controlled by genes
- Cell proliferation - Cell to cell signalling - Changes in cell shape - Cell movement - Cell death - Pattern of gene activity
Stages of apoptosis
- Cell shrinks through breakdown of cytoskeleton - Cytoplasmic density increases, sub-cellular organelles become more tightly packed - Chromatin is condensed - Nuclear envelope membrane breaks down, DNA fragments - Cell membranes forms buds - Cell is broken into vesicle structures, which are phagocytosed
What processes are required during development?
- Cell to cell communication - Cell shape changes - Cell movement - Cell proliferation - Cell death
Modern cell theory
- Cells contain hereditary information that can be passed on - All cells are essentially comprised of the same chemical mix - Cells can carry out all the basic chemical and physiological processes within themselves - Cellular activity depends on the activities of sub-cellular structure
Describe cell movement and differentiation in gastrulation
- Cells of the epiblast migrate towards the primitive streak - Upon arrival in the regions of the streak, they become flask shaped, detach from the epiblast and slip beneath it - This inwards movement is known as invagination - As gastrulation proceeds, primitive groove extends anteriorly Process 1. Cells remaining in the epiblast then form ectoderm 2. Other cells come to lie between epiblast to form mesoderm 3. Once cells have in-vaginated, some displace hypoblast - Endoderm
Explain what occurs during early implantation
- Cells of the inner cell mass become epithelial like, and delaminate to form two layers (bilaminar germ disc) - Upper (dorsal) layer = epiblast - Lower (ventral) layer = hypoblast
Explain the developmental details of notochord around d19-21
- Cells that enter the primitive streak at the primitive node, migrate cranially to form the chordal process - Grows longer through proliferation of the primitive node cells at its front end up to the prechordal plate - At the same time, the primitive streak recedes back in the caudal region
What is the function of the sertoli cells?
- Cells that support spermatogenesis - Form the blood-testis barrier so immune cells don't kill off germ cells - Sex determination - sertoli cells of testis express SRY gene - Anti-mullerian hormone - drives removal of female reproductive systen in embryo - hormonal regulation - inhibin and activins - stem cell regulation
What is the morphogen gradient
- Cells will differentiate depending on the concentration of the morphogen gradient that diffuse between cells using paracrine signalling - these molecules include (TGFbeta + Hh/Shh + WNT + FGF(8)(R)) - Location of cell within organism influences how that cell will divide and differentiate
Steps of endochondral ossification
- Chondrocytes proliferate and form large aggregates of cartilaginous tissue - Cartilage matrix surrounding hypertrophied chondrocytes become calcified, depriving chondrocytes of nutrients and undergo apoptosis - The remaining matrix acts as a base for bone deposition - Osteoblasts secret osteoid - Ossification proceeds outwards
Growth plate zones
- Chondrocytes → Proliferate → Hypertrophic Cartilage → Chondrocyte Apoptosis → Ossification o Chondrocytes undergo proliferation and therefore enter cell cycle o Proliferation, then maturation (hypotrophic) increase in size 4-10 times o Chondrocyte to maturation process driven by Hh o Chondrocytes undergo apoptosis then bone is made - Note: this must occur with perfect symmetry in the limbs on both sides of the body
Describe Anaphase
- Chromosomes separate and move towards the poles
What are the fundamental processes of development?
- Cleavage division - Pattern formation - Morphogenesis - Growth - Cell differentiation
Six stages of development
- Cleavage divisions - Pattern formation - Morphogenesis - Cell differentiation - Growth
Describe early mouse development
- Cleavage is asynchronous - Cleavage is rapid - Slower in mouse and humans compared to fish and frogs
Types of fibres (3)
- Collagen Fibres: By far most abundant - Elastic Fibres: Found where tissue can be stretched (ear cartilage) - Reticular Fibres: Type of collagen
Describe testes-testosterone production
- Communication with brain - Leydig cells sit outside the seminferous cord, produce testosterone - endocrine communication
Why are bones composed of both compact and trabecular bone?
- Compact bone helps bone resist compression, while trabecular bone helps act as shock absorbers - Don't want bones to be too heavy - Trabecular gives space for our bone marrow, to support RBC formation
Describe prophase (4)
- Condensation of chromosomes - Nuclear envelope disappears - Centrioles move to the poles - Recombination (crossing over) over causes variation in alleles
Bone marrow in adults consists of...
- Connective tissue stroma of reticular cells and fibres in a meshwork - Islands or cords of haemopoietic cells - Fat cells - Macrophages - Megakaryocytes - Sinusoids
Procedure to make a knockout mouse
- DNA construct is introduced into ES cells - Colonies of ES cells containing the desired modification are selected for - ES cells are injected into a host blastocyst and transplanted into a foster mother - Chimaeric animals are born, then can be bred to produce a knockout animal
Describe synthesis (S) phase
- DNA is replicated to produce two identical copies of each chromosome - Replication begins at many sites - pre-replication complexes which speed up the process - It is checked for incorrect copying or mutations.
Identify the series of genes whose overexpression results in learning and memory deficits in DS
- DYRK1A (transcription factor - signaling) - synaptojanin 1 (neuronal communication) - single-minded homologue 2 (SIM2) (master regulator of neurogenesis)
Reticular fibre
- Delicate, fine networks - Type of Collagen - Visible in histological sections - Give support to individual cells
Dense connective tissue Describe its ECM
- Densely packed collagen fibres - Cells are sparse
What happens around 7 days prior to ovulation?
- Dominant follicle is define - 50 follicles start maturation process but only 1 dominates - Dominant follicle enlarges, becomes FSH independent and secretes high levels of inhibin, which supresses pituitary FSH production - causing semi matured follicles (other 49) to degenerate - KNOWN AS ARTRETIC FOLLICLES
Dwarfism
- Dominant mutation in FGFR3 causes defects in bone growth - Shown to be associated with advanced paternal age
Describe how transplantation experiments identified the dorsal lip as signalling centre responsible for patterning the embryo
- Dorsal lip transplanted on opposite side of embryo - Induce whole 2nd axis - Dorsal lip is a signalling centre, which when implanted, organises tissue around it - Result is 2 diff embryonic axis
Mouse research disadvantage
- Early acting mutant phenotypes difficult to study - Embryonic manipulations are difficult - Development and life cycle relatively slow (months) - Relatively expensive to maintain - Responses to therapeutics not always consistent with human - Physiology of a SMALL animal - Strict ethics
Elastic cartilage
- Epiglottis, Larynx, External Ear and Auditory Tube - Persists into adulthood
Major cells making up connective tissue (4)
- Fibroblasts - Chondrocytes - Osteoblasts - Adipocytes
What cells are in dense connective tissue?
- Fibroblasts (fibre-forming cells)
What is the notchord?
- Flexible rod like structure - Main longitudinal structural element (in early embryo) - Serves as the axial skeleton of the embryo until other elements such as the vertebrae form
Special features of RBC
- Flexible, flattened (for better oxygen diffusion) - Disk shaped cells - Don't have a nucleus - Flexibility allows it fit through tiny capillaries
Ovarian cycle consists of
- Follicular phase and ovulation - Luteal phase ovulated follicle remnant
Ovarian cycle consists of?
- Follicular phase(estrogen)& ovulation - Luteal phase(progesterone) ovulated follicle remnant (corpus luteum) produce progesterone in preparation for pregnancy
What does loose connective tissue form?
- Forms a close association with epithelium (e.g. gut): Vascular and nerve supply - Forms a "packing material" for the body (fat), and semi-solid fel and fibres for tissue support
The hypoblast: - Forms: - Gives rise to:
- Forms primitive/parietal (extra-embryonic) endoderm that lines the yolk sac - Also gives rise to extra-embryonic (splanchnic mesoderm)
Therapeutic outcomes for Down syndrome
- Found in Ts65Dn mice treated with anti-depressant Prozac (during development), there were significant improvements in neurogenesis in the hippocampus. - Treating Ts65Dn during gestation with two neuroprotective peptides reduces the delay in acheiving developmental milestones in babies - In mice also, picrotoxin improved hippocampal-based learning
Hyaline cartilage found where?
- Found in trachea and Bronchi - Found at the end of bones and inside synovial joints (resist compression)
Where is elastic fibre found?
- Found where tissue can be stretched
Depending on the signal and nature and state of the receiving cell, the effectors can be?
- Gene regulatory proteins - Ion channels - Components of a metabolic pathway - Parts of the cytoskeleton
Gene expression is regulated at several different levels
- Gene transcription - Selective nuclear RNA processing - Selective messenger RNA translation - Differential protein modification
How is gene expression regulated?
- Gene transcription - Selective nuclear RNA processing - Selective messenger RNA translation - Differential protein modification
ECM components
- Glycoproteins: Proteins with Carbohydrates - Proteoglycans: protein cores with sugar units - very hydrated - Hyaluronic Acid: long chain of sugar molecules
Role of microfilaments (overview)
- Helps in cytokenesis - Muscle contraction - Cell shape - Plasma membrane support
Attachment of the cells basal surface
- Hemidesmosome
Placental function
- Hormone synthesis and secretion; hCG, progesterone and estrogens - Growth factor synthesis and secretion, which act on placenta, fetus and the mother
Hypoblast
- Hypoblast: spreads out and covers the blastocoel to form yolk sac - extra embryonic tissue produces blood cells, and will form placenta
Neurotrophin role
- Important for neuronal survival - Axon guidance - Helps establish synapses and form mature synapses Different neurotrophins have different effects on axon outgrowth depending on the cell
What happens to intestinal tract when you inactivate or overactivate notch?
- Inactivate- end up with intestinal tract full of secretory cells and lack absorptive cells - Overactivate notch - end up with the opposite
Elastic fibre
- Individual microfibrils embedded in matrix - Matrix = 90% of the fibre - Composed of protein elastin
Beige Adipose Tissue
- Inducible cell type that is dispersed throughout white adipose tissue
Fibrocartilage found where?
- Intervertebral discs
What are the defining properties of a stem cell?
- It is not itself terminally differentiated - It can divide without limit (for the animals lifetime) - When it divides, each daughter cell has a choice to remain a stem cell or begin a course that leads to terminal differentiation (asymmetrical division)
Explain regulation of somitogenesis
- It is thought that waves of signalling factors drive the budding off process in somitogenesis - Hox Gene Patterning - Somites are specified along the anterior posterior axis - Notch Signalling - Determines placement of somite formation
Describe process of heat production
- Liberated fatty acids of multilocular adipocytes are quickly metabolized, with a consequent increase in oxygen consumption and heat production, elevating the temperature of the tissue and warming the blood passing through it.
How can you visualise cellular organelles?
- Light microscopy: staining - Fluoersence microscopy (confocal) - Electron microscopy - Using antibodies
Primordial Germ Cell Journey - HUMANS
- Little is known of earliest stages of specification and commitment - During the fourth week of human gestation, PGCs migrate from the yolk sac and into the developing embryo - PGCs enter the gonads at Week 6-8 and will differentiate
Describe gap 1 phase (G1)
- Longest period of the cell cycle - Some non dividing cells (nerve cells) never leave this stage (G0 state) - Cell functions normally, and protein and organelle synthesis occurs - The cell doubles in size
Loose connective tissue Describe its ECM
- Loosely arranged collagen fibres, with many cells
Communication between cells is mediated by: (3)
- Mainly by extracellular signalling molecules - Long and short distance signalling - Most cells both emit and receive signals
Describe how adipocytes affect hormone biosynthesis and fertility
- Male adiposity has a significant impact on fertility e.g. more likely to be infertile if overweight - Testosterone impacts adipocyte proliferation, differentiation and fat distribution
What happens 10-12 hours before ovulation in maturation
- Meiosis resumes - Theca cells produce lutenising hormone (LH) receptors and respond to LH stimulus from the pituitary. - Granulosa cells also produce LH receptors to respond to the LH surge from the anterior pituitary, which triggers ovulation
How to test if a cell is really a stem cell?
- Mice irradiated - Receive transplant of hemopoietic SC from healthy donor - Repopulates cells in bone marrow - It is possible to genetically modify defective cells in culture and replace in an animal (ex vivo, and retransplanted)
Describe paracrine signalling
- More common than contact dependent signalling - Function by binding to a receptor that initiates an enzymatic reaction - Very common in development - Signalling cells secrete signal molecules into the extracellular fluid - May be carried far away or act in the local environment - Usually the signalling and target cells are different cell types - Molecules must not be allowed to diffuse too far - Therefore - Often rapidly taken up by target cell, destroyed by enzymes, immobilised by ECM or the activity is blocked by secreted protein antagonist - Embryo uses the same proteins to construct the organs
Structure of collagen
- Most abundant - Tough and flexible - Resist stretching
What do the mullerian ducts develop into?
- Mullerian ducts fuse - Form Fallopian tubes - uterus, and vagina - and the Wolffian ducts degenerate
Describe synaptic signalling
- Nerve signalling in the nervous system - Neurotransmitters released from one nerve to target cell
Describe telophase (3)
- Nuclear envelope reforms around chromosomes - Cell begins to split, forming haploid daughter cells - In Meiosis 2 - Microtubules of the spindle, attached to the chromatids, pull them in opposite directions
Important aspects of the nucleus
- Nucleoplasm - Nuclear envelope - protective membrane - Nuclear pores - protein trafficking - Nucleolus - site of ribosome assembly
Describe the process of notochord formation from the mesoderm
- Once mesoderm is generated through gastrulation, it begins to specialise - i.e. specific regions of the mesoderm generated become molecularly and morphologically distinct - Notochord is generated through chordamesoderm which is the direct antecedent of the notochord - Chordamesoderm sits immediately beneath the developing central nervous system - Mesodorm folds and neural groove forms, eventually folds to become notochord with neural tube sitting right above
Describe colonisation
- PGC's colonise the gonad and undergo sex determination - Oogonia enter meiosis, but arrest at Prophase 1 of meiosis til puberty - Gonocytes undergo mitosis-arrest-mitosis, and don't enter til puberty
Describe migration
- PGC's undergo both passive and active migration to the gonads - Extensive proliferation occurs during this migration
Major roles of notochord
- Patterning the neural tube - Reinforcement and maintenance of events during gastrulation (e.g. left right asymmetry)
Function of UCP1
- Permits the backflow of protons previously transported to the intermembrane space without passing through ATP-synthase during oxidative phosphorylation - Consequently, the energy generated by proton flow is not used to synthesize ATP and is dissipated as heat.
Defects associated with NCCs
- Pigmentation defects (trunk and cranial NCC) - Peripheral nerve tumours - Defects in vagal NCC, enlarged colon
Where is the notochord positioned?
- Positioned centrally in the embryo, with respect to both the dorsal-ventral and left right axes
Craniosyniosynostosis
- Premature fusion of sutures of the cranium - Caused by mutations in FGFR1 and FGFR2
Describe endocrine signalling
- Production of hormones secreted into blood stream - Act at really low concentrations because they're travelling large distances - Important in sex determination, puberty, brain development
Proportion of cells and ECM?
- Proportion of cells is in the minority - Extracellular material dominates (protein rich)
What are the functions of epithelial cells?
- Protection (of tissues) - Absorption (in gut) - Secretion (sweating) - Excretion
Medical complications of obesity
- Pulmonary disease - Nonalcoholic fatty liver disease - Osteoarthritis - Skin - Gout - Cancer - Stroke - Coronary heart disease
What is required for successful implantaion?
- Receptive endometrium (secretes right factors that attracts the blastocyst, adhesion factors) - Good quality embryo
Hyaline cartilage role
- Resist compression, is flexible and keeps airways open
Describe interphase (2)
- Resting Phase - Dna is already replicated
Similarities between white and brown AT
- Rich blood supply
How does SRY determine male sex determination?
- SRY gene located on the Y Chromosome, when switched on, - Switches on a cascade of genes responsible for male gonadal development - Causes the male gonads to form
Model organisms for gastrulation study
- Sea urchins (fluid filled, see through) - Chicken (have very similar morphology with humans)
The fetus is considered to be what 2 things?
- Semi-allograft - Fetus immunologically distinct from the mother
Describe testis "cord" formation
- Sertoli and germ cells localise to the inside of the cords - Other somatic cell types including immune cells localise to the interstitium - Cords are separated from interstitium by basement membrane and peritubular myoid cells - This creates the niche that maintains spermatogonial stem cells and will later direct the progression of spermatogenesis.
Function of sertoli cells? - Sex determination - Developmental - Hormonal regulation - Stem cell regulation
- Sex determination: Express SRY - Developmental: Anti-Müllerian hormone (AMH) - early stages of fetal life. - Hormonal regulation: Inhibin and activins - regulate FSH secretion after puberty - Stem cell regulation: GDNF - ensures self-renewal of spermatogonial stem cells
Role of the cytoskeleton
- Shape - Support - Movement (of the cell, organelles)
Describe contact-dependent signalling
- Signalling molecule remains bound to surface of signalling cell - Influence only cells that contact it - Very important in development - Communicating cells may send long cytoplasmic processes to contact each other - Can cause cells to differentiate into different cell types - precise spatial patterning - Promote apoptosis in cells
Environmental Assymmetry
- Signals from the environment direct cell fate. - Concept of a Stem Cell niche - Niche can regulate the balance between self renewal and differentiation.
Advantages of Drosophila
- Simple genome, only four chromosomes - Very inexpensive - Quick breeding, generation times are very short
Importance of testis integrating skin and nerves
- Skin - epithelial layer - Superficial somatic afferents: Epidermis - no nerve fibres , Dermis - rich supply of peripheral nerves
Describe the potential therapeutic applications of ES cells and some of the limitations
- Skin cell from adult, transplant nucleus of SC into oocyte, oocyte develops into blastocyst where ICM can be taken and can be used to produce ESC - Genetically identical to donor who provided the skin sample - Ethical limitations
Function of BAT?
- Small lipid droplets, abundant mitochondria, and rich vasculature all mediate brown fat energy demand. - Heat production by non-shivering thermogenesis
Primordial germ cell journey - summary
- Specification - Commitment - Migration - Colonisation (includes sex determination)
What distinctly different features do oogenesis and spermatogenesis have?
- Spermatogenesis has equivalent meiotic divisions resulting in four equivalent spermatids - Oogenic meiosis is asymmetrical: only one egg is formed together with three polar bodies. - Different timing of maturation
How can stem cell division can result in caner?
- Stem cell fails to produce one non-stem cell daughter in each division. They therefore proliferate, and form a tumour. - Daughter cells fail to differentiate normally and instead proliferate to form a tumour.
Describe spermatogenesis
- Takes place in testis - Mature in epididymis - Goes through ducts, seminal vesicle, prostate gland and out through penis - Needs to occur lower than body temp
What is the primitive streak? i.e. what does it look like and what days does it occur?
- The formal process of gastrulation begins with formation of the primitive streak in the surface of the epiblast - Initially, the streak is vaguely defined, but in 15-16 days, it is clearly visible as a marrow groove with slightly bludging regions on sides - The cephalic (head) end of the streak, the primitive node, consists of a slightly elevated area surround the small primitive put
Describe what happens in maturation in terms of: - Theca cells - As puberty approaches - Size
- Theca cells initially secrete an angiogenic factor, which stimulates blood vessel formation in the layer, to support growth of the follicle - As puberty approaches, Follicle stimulation hormone (FSH) produced in pituitary - Acts for the formation of the antrum (liquid-filled cavity) - Increases in size through granulosa cell proliferation in response to locally produced actin
What is the urogenital crest involved in intermediate mesoderm fate
- This more elongated structure called urogenital crest, and is the origin of the kidneys and gonads
Epithlial cells attachment on the cells lateral surface
- Tight junctions (zonula occludens) - Zonula adherens - Desmosone (macula adherens) - Gap junctions - Infoldings of membranes
Mechanisms are required: (2)
- To control which signals are emitted and when they are emitted - To enable the signal-receiving cell to interpret the signals
What are somites? what are they responsible for?
- Transitional Embryonic Structures - Responsible for segmental organisation of the embryo
Fibrocartilage role
- Transitional between dense connective tissue and hyaline cartilage - Tough and resists compression - Collagen type I dominant
Describe the storage and mobilisation of lipids
- Triglycerides are transported by lymph and blood from the Intestine and liver in lipoprotein complexes known as chylomicrons and very low— density lipoproteins (VLDLs). - In capillary endothelial cells of adipose tissue, these complexes are partly broken down by lipoprotein lipase, releasing free fatty acids and glycerol. - The free fatty acids diffuse from the capillary into the adipocyte, where they are re—esterified to glycerol phosphate, forming triglycerides. - These resulting triglycerides are stored in droplets until needed
Zebrafish advantages
- Vertebrates - 70% of human genes have a zebrafish counterpart - 84% of known disease-causing genes have a orthologue in zebrafish - the female fish spawn eggs that are externally fertillised, so embryonic development occurs externally and is easily accessed visually - rapid embryonic development - can induce mutations by adding substances to the water
Describe RB protein
- When RB is inactivated by phosphorylation, genes can now be transcribed to allow the cell to enter S-phase - If Rb is inactivated, it cannot stop the cell cycle - Causes retinoblastoma
Wnt
- Wnt is vital for the maintenance of stem and progenitor cells in the crypt - As wnt moves out, no cell proliferation as cell signal stops, and the cell differentiates
What are the phenotypic outcomes in this mouse model?
- altered craniofacial development - memory and learning deficits - age-related alterations in the forebrain
Extracellular Matrix (ECM) may form...
- an insoluble barrier or connection between tissues - a loose network in which cells are scattered - a substratum which cells bind to and form a sheet (e.g. epithelial cells on a basal lamina) - a substratum over or through which cells migrate
Plasma membrane
- fluid mosaic model - separates living cells from nonliving surroundings - incorporates receptors that allows the cell to respond to signals from outside
What is sertoli cell only syndrome?
- no germinal epithelium - Failure of Sertoli-germ cell communication etc
Smooth ER
- no ribosomes - site of carb metabolism, ion regulation, synthesis and metabolism of steroids and lipids, and some drug detoxification
Examples of when apoptosis is needed
- remove damage cells - digit formation - creation of hollow tube in epithelial tubular
List the steps of primordial germ cell journey (in mice)
- specification - commitment - migration - colonisation
Dartos muscle
- temperature regulation - smooth muscle that produces the wrinkled surface of the testis (and labia majora in females)
Rough ER
- translation of mRNA into proteins by ribosomal complexes - production and processing of specific proteins
How long are microvili?
1 micron
What underlies genetic variation?
1) Crossing Over - ensures shuffling of the alleles 2) Independent assortment - homologues line up and cross randomly on the metaphase plate in Meiosis I 3) Random fertilisation - ovum has 8 million possible chromosome combinations and so does each sperm = 64 trillion possible
What regulates vasculogenesis?
1) Fibroblast growth factor 2 (FGF2) - required for generation of heamangioblasts from mesodermal cells 2) Vascular enothelial growth factor (VEGF) - Promotes proliferation and differentiation of angioblasts to from endothelial cell tubes. - If it is knocked out, yolk sac lacks blood vessels and dies 3) Angioproteins - Mediate interactions between endothelial cells and pericytes, forms the blood vessel walls - Knocked out mice will have malformed blood vessels
How do we make cartilage?
1) Paraxial mesoderm forms somites, gives rise to the sclerotome from which cartilage is derived. These cells undergo ossification via endochondral ossification 2) Cranial NCC form bones through intramembranous ossification. NCC cells condense and change shape to form osteoblasts
Fertilisation summary
1) Sperm-egg recognition 2) Acrosome exocytosis 3) Zona penetration 4) Sperm fusion 5) Block to polyspermy (fusion, penetration, binding)
Methods to find out a cells fate
1) Using tracer dyes or fluroescent markers, see where the cells move and develop into. Only works for a short period of time if that cell becomes thousands of cells 2) Genetic methods
Which cytoskeletal filaments are critically important for 1) cell migration, and 2) intracellular movement of organelles?
1) actin microfilaments, and 2) microtubules
Key stages of implantation
1. Blastocyst hatching from the zona pelluicda 2. Blastocyst apposition to the uterine wall 3. Attachment of trophectoderm (blastocyst outer layer) to the uterine wall 4. Blastocyst invasion into the uterine wall
Key stages of implantation
1. Blastocyst hatching from the zona pelluicda 2. Blastocyst apposition to the uterine wall 3. Attachment of trophectoderm to the uterine wall 4. Blastocyst invasion into the uterine wall
What does the uterus consist of?
1. Body 2. Fundus (top) 3. Cervix (neck) 4. Uterine cavity 5. Cervical canal
Goal of the cell cycle is to produce genetically identical cells from one precursor cell, which is accomplished through (2)?
1. Cell duplicates its contents - Replication of DNA and accurate separation of chromosomes - Doubling of cell mass 2. The cell physically divides in two - Each daughter cell receives a copy of the entire genome - Each cell receives half the cell contents (so that cells do not reduce their size upon division)
Describe the sequence of programmed cell death (apoptosis)
1. Cell shrinkage and rounding through caspase-mediated breakdown of cytoskeleton 2. Cytoplasmic density increases, and subcellular organelles become more tightly packed 3. Chromatin undergoes pyknosis: a process of condensation, and localisation to the nuclear envelope 4. The nuclear envelope itself then undergoes karyorrhexis, where the DNA is fragmented, and the membrane is broken down 5. The cell membrane starts to form buds, or "blebs" 6. Ultimately, the cell is broken down into vesicle structures - are phagocytosed
Progressive stages that are universal between organisms (5 stages)
1. Cleavage divisions 2. Pattern formation 3. Morphogenesis 4. Cell differentiation 5. Growth
Describe G1-S Phase Control and the regulatory molecules involved
1. Cyclin D is produced, and binds to CDK4. Through a complex pathway, this results in the transcription of genes including cyclin E 2. Cyclin E-CDK2 complexes bind and activate, preparing the cell for S phase 3. Levels of the transcription factors that promote the expression of the S-phase cyclins and DNA synthesis enzymes increase 4. Levels of the molecules involved in inhibition of entry into S phase are decreased (controlled degradation)
Identify and describe the 3 layers of the uterine wall
1. Endometrium: closest to the uterine cavity, innermost lining of uterus, undergoes cyclic changes due to hormones, where the embryo implants, shed during menstruation 2. Myometrium: middle layer, consists of smooth muscle cells, contractions in the muscular wall of the uterus push out the fetus 3.Perimetrium: outer layer for protection
Controllable parameters of stem cell
1. Frequency of stem-cell division 2. Probability of stem-cell death 3. Prob. that stem cell daughter will become a committed progenitor clel of the given type 4. Division cycle time of committed progenitor cell 5. Probability of preogenitor-cell death 6. Number of committed progenitor cell divisions before terminal differentiation 7. Lifetime of undifferentiated cells
What are the 3 stages of the uterine cycle
1. Menses - endometrium is shed 2. Proliferation & regeneration 3. Secretory activity increases to facilitate receptivity MPS
Uterine cycle
1. Menses - endometrium is shed 2. Proliferation and regeneration 3. Secretory activity increases to facilitate receptivity
How do the primitive and definitive phases of haemopoiesis differ?
1. The timing of haematopoiesis 2. Their sites of blood cell production 3. The morphology of the cells produced 4. The type of globin genes active in red blood cells (erythrocytes)
Procedure for creating transgenic mice by pronuclear injection
1. Tissue specific promotor: Inject gene into pronucleus of a fertilized egg 2. Gene of interest: Transfer zygote into host animal 3. pA: Transgenic mouse born
The six characteristics of epithelial cell
1. Very little space between cells 2. Strong attachments between cells - intercellular junctions 3. Surface specialisations 4. Oriented/polarised - Free apical surface and adhere to basement membrane 5. Avascular (but have nerve endings) 6. Sit on a basal lamina
Adipose tissue % in men
15 - 20%
% of adipose tissue in men (body weight)? and women?
15-20% 20-25%
When was Down syndrome first formally described and by who?
1866 By John Langdon Down
Optical projection tomography
3D models
At which stage or number of cells of the early embryo is it thought that cell specialisation has begun, in other words, when is it that cells of the embryo are no longer "equal"?
4 cell stage
At how many days does the process of sex determination begin in humans? (i.e. expression of SRY is first detected)
41-44 days in humans
What percent of down syndrome is caused by translocation?
5%
What is the average IQ of a young adult with DS
50
In humans, how long does it take from fertilisation to hatching/implantation?
6-8 days
Inorganic bone extracellular matrix
63% is hydroxyapatite crystals composed of calcium phosphate Traces of other minerals and ion Strong and can withstand compression
How long are sperm motile for after insemination
7 days
Morula stage
8 blastomeres Hard shell around, so shells become more compacted.
At how many weeks in human embryo are these ducts seen?
8 weeks
Percentage of Down syndrom causes
88% - Maternal origin of non-disjunction 9% - Paternal origin of non-disjunction 3% - Mitotic issue in the embryo
Migration by Cilia and Flagella Describe micrtotubule arrangement
9+2 to 9 fused pairs of microtubules on outside of a cylinder, and 2 unfused microtubules in centre - dynein arms attach to microtubules serve as molecular motors
Construct
A circular piece of DNA It has some regions that are necessary for its replication, as well as sites into which you can insert other genetic sequences
Zona pellucida
A coating around the egg filled with proteins Sperm has to break through it so it can fuse with the egg
Maternal effect genes
A gene that, when mutant in the mother, results in a mutant phenotype in the offspring, regardless of the genotype.
Neural crest cell (definition)
A group of cells that originate at the dorsal part of the vertebrate neural tube It can give use to a wide range of differentiated cell types Referred to as the 'fourth primary tissue'
Morphogen
A growth factor, which diffuses between cells and has a different effect on a cell depending on its concentration
Plancental anchorage
A major role of the placenta is to anchor itself to the uterine wall via cytotrophoblasts
UCP-1
A marker unique for brown fat
Testicular torsion
A medical emergency, where the blood supply is broken in one of the testis and it is without blood supply. Have to have surgical untwisting of the testis, within 12 hours or necrosis occurs
Allantois
A membrane repository for urinary waste in many vertebrates In humans, its mesodermal wal of the structure gives rise to blood vessels supplying the placenta
What determines the digit pattern in a developing chick?
A morphogen gradient Experiments show when you transfer part of the limb (polarising region) and transplanted it to the anterior part of another limb. Resulted in a duplication of the chick limb Different threshold amounts cause the formation for each of the digits. If you transplant the polarising region, you get two opposing thresholds - results in duplication
Chimaeric mouse
A mouse generated from a mouse blastocyst comprising cells from 2 different mice
p53
A negative regulator of the cycle It acts to activate the transcription of inhibitiors of cdk/cyclin kinases It blocks the transition of the cell from G1 to S It is the tumour supressor gene
Defect experiment
A portion of the embryo is destroyed and the impact on subsequent development is observed.
Repressor
A protein that suppresses the transcription of a gene.
What is an erythrocyte?
A red blood cell
C. elegans
A round worm Used particularly for nervous system development - only has 320 neurons Also fate mapping the WHOLE of development as very single cell could be tracked
What is the cause of intellectual disability?
A series of genes have been identified, where over-expression results in learning and memory deficits. These include DYRK1A (transcription factor) synaptojanin 1 (neuronal communication).
Spemann organiser
A signalling centre that is responsible for patterning the embryo, located in the dorsal lip During gastrulation, if it is transplanted into another embryo it can induce a whole secondary axis.
What is adipose tissue?
A specialised type of connective tissue in which adipocytes or fat cells predominate
Adipose tissue
A specialized type of connective tissue in which adipocytes or fat cells predominate.
Determination
A stable change in the internal state of a cell Tissue is committed and fate cannot be reversed, even when placed in a different region of the embryo Transplantation experiments can test when a cell is determined
Determination
A stable change in the internal state of a cell. Tissue is committed and fate cannot be reversed even when placed in a different region of the embryo. It forms into whatever its host or original fate is
Alzhemier's disease and Down syndrome
A strong correlation between Down syndrome and the development of Alzheimer's disease. The amyloid precursor protein AAP gene was localised to Cr21. By 40, most DS people have a type of dementia similar to Alzheimer's.
What is involved in a simple positive feedback loop in gene regulation?
A transcription factor will promote further expression of itself.
Lysosome
A vesicle, produced by the Golgi Contain a variety of digestive enzymes "suicidal bags of the cell"
Eosinophils
A white blood cell containing granules that are readily stained by eosin. Restrains the intensity of inflammatory reactions Involved in allergic disorders and asthma
Describe the cortical reaction
AKA the slow block - There are cortical granules under the egg membrane which contain hydrolytic enzymes - Ca2+ release into the egg stimulates the cortical granule response - Cortical granules release their contents into the space between the cell membranes and the vitelline envelope (ZP) - This results in hardening of the vitelline envelope (egg surface) and permanently blocks further sperm from binding; usually point at which sperm fall off
Thrombocytopenia
Abnormally low numbers of platelets in the blood
Functional redundancy of skeletal muscle genes
Absence of a single myogenic regulatory factor alone doesn't prevent the formation of skeletal muscle But when BOTH are knocked out, muscle fails to form
Describe how different cells can respond differently to the same signal, using ACh as an example
Acetylcholine binds to different receptors to induce different responses - Heart muscle - Decreased heart rate and force of contraction - Skeletal muscle cell - Muscular contraction - Salivary gland cell - Secretion in salivary gland
Key proteins in skeletal muscle
Actin Myosin
What cytoskeletal elements are required for neuron migration?
Actin and adherins
What cytoskeletal elements are involved in axon guidance?
Actin microfilaments and microtubules
Transfer ES cells with the targeting construct
Add the plasmid reagent, so it will introduce resistance to some cells that take it up Then add the antibiotic, will destroy ES cells without the resistance
What are cadherin proteins needed for?
Adherens junctions
How does the epithelial sheet change shape?
Adherens junctions Epithelial sheet is invaginated by tightening adhesion belts with associated actin filaments, pinches off from overlying sheet of cells
Leptin
Adipoctyes are the sole source of leptin Regulates appetite under normal condition, and regulating the amount of adipose tissue
Cell types in white adipose tissue
Adipocytes are 30% Preadipocytes and fibroblasts Matrix of collagen fibres Blood vessels (capillaries/endothelial cells) Immune cells (macrophages, lymphocytes)
Types of connective tissues
Adipose tissue Cartilage Bone Blood Loose connective tissue (under the skin) Fibrous connective tissue (forming a tendon)
Subcutaneous adipose tissue
Adipose tissue located under the skin Abdominal, femoral
Types of stem cells
Adult stem cells Embryonic stem cells iPs cells
Confocal microscopes
Advantages to standard microscope, as the light goes all the way through the sample, refracting and diffusing resulting in a blurry image. Confocal microscope uses mirrors to focus, resulting in a clearer image Uses fluorescent stains
Blastocyst vs embryo
After the blastocyst is implanted into the uterine wall, it is then referred to as an embryo It is the embryo that undergoes gastrulation
When is sex determined for PGCs?
After they have entered and colonised the gonad, as it has already recieved signals on what it will develop into
Function of platelets
Aggreate at discontinuities in vessel wall to form a plug This forms a blood clot
Adherens junctions
Aka Zonula adherens Provide some adhesion between cells, encircles the cell Connect to actin microfilaments (in a bundle) Actin filaments are joined by cadherins
What cell types do we need for a testis?
All of them! In most organs, all of the cell types except for the gonocytes will be involved
What is the developmental progression that a RBC undergoes?
All red blood cells are formed from the mesoderm, the middle germ layer.
Focal adhesions
Allow adhesion of the cell to extracellular matrix, where actin filaments insert into plaques on the cytoplasmic surfaces
Single-cell migration
Allows cells to cover local distances and integrate into tissues Or to move from one location in the body to another and fulfil effector functions But during cancer, this means it can metastasis to distant sites
Why do blood vessels follow peripheral nerves?
Allows the nerves to get oxygen and for hormones in the blood to regulate vasoconstriction and vasodilation Nerves also secrete VEGF which is necessary for artery formation
Altered plane of division
Altering the plane of the division (e.g. horizontal instead of vertical) Done through the mitotic spindle Regulates asymmetrical cell division
Diagnostic tests for foetus
Amniocentesis Chorionic villus sampling They are invasive, and there is a risk to the foetus
Extraembryonic membranes
Amnion = fluid filled exxtraembryonic tissue, provides a buffer from mechanical injury Yolk sac = extraembryonic hematopoisis Allantois = functional respiration role by vascularising other membranes
How a single signal works
An extracellular signal molecule binds to a receptor protein the plasma membrane. Intracellular signalling proteins occur, acting on effector proteins. Effector proteins downstream can lead to many alterations in cellular behaviour (e.g. gene regulatory proteins, metabolic enzyme)
coronal plane
An imaginary plane where the body is cut into front and back parts.
Beige adipose tissue
An inducible cell type, dispersed throughout white adipose tissue Has greater variability in lipid droplet size and a greater proportion of lipid droplets to mitochondria - giving it a light brown appearance
Example of homeotic transformation
Antennapedia mutation Legs grow out of the head region!
Describe establishment of asymmetry (A, B and C)
Anterior-Posterior and Dorso-ventral Axes A: The second polar body marks the anterior (animal pole) and also determines the first cleavage B: The dorsal ventral axis forms at right angles to the A-P axis Gastrulation - The third L/R axis is defined by the first two axes
Establishment of asymmetry
Anterior-posterior axis is formed, determined by the first cleavage The dorsal-ventral axis forms at right angles to the A-P axis
What happens when Ts65Dn mice are treated with fluoxetine (Prozac)?
Anti-depressant a serotonin reuptake inhibitor, significant improvements in the levels of neurogenesis in the adult hippocampus are observed
Germ cells
Any cells that gives rise to the gametes of an organism that reproduces sexually Only cells that can undergo meiosis (and mitosis)
Where does definitive haemopoiesis occur?
Aorta-gonad-mesonephros (AGM) region But ultimately occurs in the liver, placenta, spleen and bone marrow
Asymetric hypothesis
Appears to be the case Individual blastomeres in early embryos are NOT equivalent
Blastocyst implantation
Apposition (blastocyst floating around) Attachment Invasion
Platelets structure
Are non-nucleated, disk-like cell fragments 2-4 microns Survive for about 10 days in bloodstream
Two cell embryo questions
Are these cells the same? Cells can look very similar but not actually be the same
What is the lateral plate mesoderm
Are thin extremities of intermediate mesoderm
What is the fluid or ground state?
Area between any of the solid aspects
Where is cartilage form?
Areas where compression/load is resisted. Needs structure, but flexibility
Where does intraembryonic vasculogenesis arise from?
Arises from angioblasts in the mesoderm surrounding developing organs
When does gastrulation occur?
Around 14-16 days after fertilisation
Perivascular distribution
Around vascular system
Arrangement of trabecular bone
Arranded in thin parallel struts, called trabeculae Trabeculae are ocmposed of lamellae There are no blood vessels present = meaning there are no osteons
How does the neural plate develop?
As the notochord (mesoderm) develops (prechordal and cranial portion of the chordal plate), it begins to exert an inductive effect on the ectoderm that lies above it by secreting factors. These cells become neuroectoderm and form the neural plate
Induction of neural plate
As the notochord develops, it exerts an inductive effect on the ectoderm to specify it. These cells become neuroectoderm and form neural plate Day 19
Types of glia clells
Astrocytes, oligodendrocytes, microglia, ependymal cells
3) Spinal disc herniation
Asymmetrical compression of the intervertebral disc ruptures the sac-like disc, leading to compression of and pain from adjacent nerves.
When does meiosis begin in male germ cells?
At puberty
Where do left/right symmetry-breaking events occur?
At the ventral surface of the node
Cell types derivate of neural crest cells
Autonomic neurons Schwann cells Melanocytes Parts of connective tissue Facial cartilage and bones Neuroglial cells
Haemangioblast
BMP acts on the mesoderm to form a hemanigoblast This gives rise to a pluripotential hematopoietic stem cell (giving rise to most blood cells) Also gives rise to angioblasts, which form endothelial cells
Epimere
Back muscles
Short range cues
Based on contact
Another name for basal lamina
Basement membrane
Osteoprogenitor
Basically bone stem cells, arise from mesenchymal stem cells First cells to commit to the bone lineage They give rise to osteoblasts Presist for life, in low abundance Most activity during growth and development, but also during damage
Why are ES cells heterozygous for mutated DNA?
Because only one allele will have undergone homologous recombination and contain the mutant, the other is wild type
Why are the mouse pups chimaeric?
Because they are a combination of normal WT cells from the blastocyst and the selected mutant embryonic stem cells.
Why can epithelial cells morph into shapes?
Because they are joined together, have an apex and a base, can proliferate They can become specialised, form branches and be multilayered
In later vertebrate development, what does the notochord become?
Become part of the vertebral column
Myf5 negative
Becomes beige preadipocyte and white preadipocyte. Depending on what genetic program occurs, they become beige or white adipocytes. White and beige adipocytes can change into one another - transdifferentation
Myf5 positive
Becomes brown adipocyte
Describe maturation of oocyte: - Before Birth - At Birth - To Puberty - What follicular cells do?
Before Birth: Cells from the ovary surround the oocyte to form the primordial follicle At Birth: Oocyte completely encloses follicular cells To Puberty: Follicle size increases due to increase in oocyte size, and number of follicular cells Follicular cells secrete a meiotic inhibitory factor responsible for maintaining meiotic arrest (released from inhibition shortly before ovulation)
Primary neuralation
Beginning stages of the nervous system
Meiosis in males
Begins at puberty, and doesn't stop
Meiosis in females
Begins during embryogenesis, and stops at prophase I. It then reinitiates at puberty in specific oocytes that begin to mature and then arrests at metaphase II Meiosis is not complete in the ovary until fertilisation has occurred
Cytotrophoblast
Beneath syntiotrophoblast, cell column
Describe the types of cancers
Benign • Enchondroma - tumor growth occurs within the bone and expands it • Ecchondroma - grows outward from the bone (less common) Malignant • Chondrosarcoma - 2nd most frequent malignant tumour of bone • Treatment - amputation as high resistance to chemo and radiation therapies
Where do cell junctions occur?
Between two cells or between a cell and the extracellular matrix
Basophil
Bilobed nucleus and granules that stain blue
Eosinophil structure
Bilobed nucleus, granules that stain red (eosin)
Ectopic pregnancy
Blastocyst implants outside of the uterus
Which term describes the cells produced by cleavage of the zygote?
Blastomeres
New diagnostic test for foetus
Blood test in first 10-12 weeks it is non-invasive Uses molecular techniques to assess aneuploidy, by targeting sequencing of autosomal chromsomes 13, 18, 21, X and Y.
What does it form in humans?
Blood vessels differentiated from mesodermal wall of allantois - form the umbilical circulatory arc, arteries and veins that supply the placenta.
Loose connective tissue
Blood, fat They allow movement, loosely arranged collagen fibres. They form a close association with epithelium
What do sertoli cells form?
Blood-testis barrier
Cell lineages. What do the following form? ICM Endoderm Mesoderm Trophectoderm
Blue: Inner cell mass - embryo proper - amnion Yellow Endoderm - Yolk sac Red: Mesoderm - Allantois Green: Trophectoderm - Cytotrophoblast - Invasive trophoblast - Syncytiotrophoblast
Intramembranous ossification
Bone develops without a cartilage intermediate
Woven bone vs lamellar bone
Bone formed during ossification, it is immature bone Collagen fibres are poorly organised and therefore weak Can be produced quickly however Woven bone is remodelled into lamellar bone, via the action of osteoclasts and osteoblasts
Mammalian stem cell niche examples
Bone marrow Intestinal crypt Mammary gland
Neuro-muscular junction establishment
Both cells need to develop specalisations Neural agrin induces ACh receptors to cluster (in muscle cell) Extracellular matrix between them established Other axons can then converge on the same synaptic site (but not all survive) Surviving axon can branch, making a complex junction. It is also myelinated
Whaat adult tissues are difficult to repair in adult life
Brain and spinal cord Pancreatic beta cells
Brain and testis relationship in behaviour
Brain influences mating behaviours (seductory, dominance behaviours) - which enable a male to mate with a female.
UCP1 positive
Brown and beige adipocytes
WAT vs BAT development origin
Brown and white have different developmental origins. Myf5 is very important and the key difference, it is the precursor cells for brown fat.
Peroxisome
Bud off from the endoplasmic reticulum Rid host of toxins and break down long chain fatty acids
Peroxisome
Bud off from the endoplasmic reticulum that can get of toxins and break down long chain fatty acids
Dense, irregular connective tissue
Bundles of collagen fibres oriented in many directions
Visceral muscle
Bundles of smooth muscle cells, connected by gap junctions They contract simultaneously when stretched beyond a certain limit E.g. intestines Derived from lateral mesoderm
Describe how epidermal SCs (ESCs) can be expanded in culture for tissue repair
Burn victims - SCs extracted, expanded in ex vivo dish, combined with scaffold to produce skin, used to replace full-thickness skin wounds.
Development of smooth muscle
By individual mesodermal cell differentiations
How can we change the expression of a developmental gene?
By making transgenic animals
What are stem cells regulated by?
By the stem cell niche - growth factors e.g. BMP4
How is the organisation of intermediate filaments determined?
By their cell type e.g. epithelial cells have int. fil distributed all over the cytoplasm and are attached to the nucleus While in primary fibroblasts, they are orientated towards the periphery and do not span the whole cytoplasm
What other tissues are immune privileged?
CNS Eye Uterus
Four marker serum test
Calculates the risk by combining the women's age and the risk estimated from serum levels of various biochemical markers. This is preliminary, done to get an indication to see if this should be done.
Issue when cilia doesn't work
Called a ciliopathies Can cause things like carniofacial abnormalities, toes fused together
Cell response to signalling
Can be fast or slow Different response to the same signal
Issues of contact-dependent signaling
Can cause cells to differentiate into different cell types Can be used to promote apoptosis in cells Used in development of many tissues
An issue in the ER function
Can cause disorders with sleep, Alzheimer's disease, MS, prion diseases etc. The disease states is when there is a decrease in normal protein folding
Pluripotent
Can give rise to cell derivatives of all three germ layers Cells that are capable of developing into most, but not all, of the body's cell types e.g. embryonic stem cells. Can't just transfer them, need to be in an embryo but once in embryo can form anything.
Totipotent
Can produce an entire organism e.g. zygote
Natural killer cells
Can recognise stressed cells in the absence of antibodies (infected cells) and kill them Play a role in rejection of tumours and virally infected cells
More leptin...
Can result to a resistant to this hormone So many of the metabolic benefits of leptin is lost Increased appetite
Trunk NCCs cell pathways
Can take very different migratory pathways Path 1 cells travel ventrally through the anterior sclerotome = become Schwann cells, sensory neurons Path 2 ***
Multipotent
Can't reproduce an entire embryo, but can form many different cells of the embryo The diversity of the cells decreases as the migration proceeds
Other names for trabecular bone
Cancellous or spongy bone
Nullipotent
Cannot differentiate any more, fully functional cell types
CO2 with haemoglobin forms..
Carbaminohaemoglobin
Three types of muscle
Cardiac Skeletal Smooth
What type of tissue does not regenerate well?
Cardiac muscle and nerves
What is the function of the vitelline vein and artery?
Carries blood to and from the yolk sac
The notochord most closely relates to what?
Cartilage
Why is cartilage blue?
Cartilage is stained blue, because alcian blue binds to polysaccharides and cartilage has a lot Bone does not have polysaccharides, so is not stained blue.
Necrosis
Caused by factors external to the cell tissue, such as injury, infection, cancer etc. Often necrotic tissue needs to be removed surgically - lack of chemical signals stop phagocytes from locating dead cells leading to a build up
Effector proteins
Cell communication generally effect these They implement change in cell behaviour Can be gene regulatory proteins, ion channels, metabolic pathway components
Why are a bunch of cells from the dorsal neural tube so important to vertebrate life?
Cell population with one of the broadest development potential It can make cartillage and bone, neurons, connective tissue, neurons, pigment cells
Gap 2 (G2) phase
Cell prepares for mitosis Synthesis of components that ensure the survival and functionality of each daughter cell
What is cartilage comprised of?
Cells + collagen fibres + protein matrix + water
Cell differentiation
Cells become structurally and functionally different from each other
Method 1 - Tracer dyes
Cells can be marked by the injection of dyes or transplantation of marked tissue - dyes will continue into development where they can be tracked in later development - this is called fate mapping
Oocyte before birth
Cells from the ovary surround the oocyte to form the primordial follicel
Example of a transplantation experiment
Cells in a blastula stage frog embryo are transplanted into another region - fate is then observed
Example of a transplantation experiment
Cells in a blastula stage frog embryo are transplanted into another region and their fate observed.
Are cells permanent?
Cells may be permanent, or they can be renewable. In renewable tissues, cells that die or are exported must be replaced. E.g. skin is replaced every four weeks, hair constantly grows, nerve cells and heart tissue are not replacable
Early implantation (day 6-8)
Cells of the inner cell mass becomes epithelial like, and delaminate to form two layers
Delamination
Cells of the inner cell mass delaminate, forming two layers = Epiblast Hypoblast
What is the role of mesenchyme during embryogenesis?
Cells of the mesenchyme are able to easily migrate through this tissue, allowing the development of structures during embryogenesis.
Connective tissue composition
Cells separated by extracellular matrix
Pluripotent
Cells that are capable of developing into most, but not all, of the body's cell types
Where does the mesoderm come from?
Cells that move through the primitive streak, lie between epiblast and endoderm
Chondrocytes
Cells that secrete cartilage matrix (ground substance) Form the cartilage tissue, that will be the template that undergoes osteophication and form bone Not capable of cell division
Skeletal muscle regeneration
Cells undergo terminal differentiation Satellite cells might be able to form fibres, so there is regneration but it is limited
Vacuole
Cellular space for water/other storage
Where is the notochord positioned?
Centrally in embryo - with respect to DV and LR axes
Triplet microtubule cylinders are...
Centrioles
Anaphase
Centromeres divide, creating two chromosomes They are drawn to opposite poles of the cell Cell elongates
Master regulator transcription factors
Certain points in development that require the presence of a 'master regulator' E.g. SRY, found on the Y chromosome. When activated, switches on a cascade of genes encoding other transcription factor
Placenta previa
Cervical implantation of the blastocyst, so the placenta covers the cervix Can be maintained throughout pregnancy, but just means that c-section is needed.
Morphogenesis
Change in form eg. gastrulation
Endometrial stromal cells
Change shape and secretory activity during decidualisation - to form the decidua during pregnancy Terminal differentiation process
Transgenic
Change the genetic constitution of an organism by genetic engineering. e.g. inserting a gene
Transgenic
Change the genetic constitution of an organism by genetic engineering. Eg Inserting a gene
Fast responses
Changes in cell movement, secretion, metabolism Need not involve changes in gene transcription May involve rapid phosphorylation of effector proteins
Fast block
Changes in membrane potential of the oocyte
Morphogen
Chemical signal whose concentration varies and is involved in pattern formation.
CiPS
Chemically induced pluripotent stem cells They can be generated from fibroblasts, but only using chemicals
Treatment for ectopic pregnancy
Chemotherapy (but needs to be early) Surgical - remove Fallopian tube
Bone marrow transplants
Chemotherapy drugs kill rapidly dividing cells - including cancer cells but also HSCs. A bone marrow transplant from a donor or their own stem cells collected prior to the chemotherapy A transplant can restore the patient's entire haematopietic system
G gallus
Chick
What cells make cartilage?
Chondrocytes
Day 22 - 25 of human ed
Chordal tissue breads away from the endoderm and the ectoderm It does this to form the notochord
Day 20 of human ed
Chordal tissue forms chordal plate by bonding with the endoderm - just for ONE day. It then separates
What else does the chordamesoderm develop?
Chordamesoderm cells develop a thick extracellular sheath and a vacuole
What technique obtains small groups of foetal tissue, with a small risk to the foetus?
Chorionic villus sampling
Prophase - early
Chromatin condenses to form chromosomes
What can go wrong with sex determination?
Chromosomal aberattions Gene-level mutations Hormones and receptors (testerone is made but receptor is mutated, Y chromosome is switched off, both result in phenotypically looking female)
Patau syndrome
Chromosome 13 trisomy - severe developmental abnormalities few survive >1 year
First cleavage
Chromosomes from egg and sperm align on a single metaphase spindle - producing two diploid cells.
Doublet microtubule cylinders are...
Cilia and flagella
How does the neural tube close up?
Closes at about the middle first, then zippers up in BOTH directions It is open on both ends
Endometrium
Closest to the uterine cavity, undergoes cyclic changes due to hormones where the embryo implants, shed during menstruation
What is a tissue?
Coherent grouping of cells Bound by cell junctions or ECM
Fibres in the ECM
Collagen Reticular Elastic
Dense, regular connective tissue
Collagen bundles oriented in same direction: resistance to stretch
Three types of fibres in connective tissue
Collagen fibres Elastic fibres Reticular fibres
Major fibre types of connective tissue
Collagen, Elastin, Reticular fibres
Describe primordial germ cell journey in humans: - Colonisation
Colonisation: − Primordial Germ Cells enter gonads at weeks 6-8 − Female Germ Cells: PCGs differentiate into oogonia when it reaches ovary, and arrest at prophase 1 of meiosis at week 12 − Male Germ Cells: PCG's form gonocytes. At birth, these become followed by intermediate spermatogonia and prespermatogonia
3D morphometric analysis
Combines different information (e.g. from ultrasound, MRI, OPT) and collect the data to make 3D images Then use this image to measure and see if the individual is developing normally or not Used for down syndrome detection
Sickle cell anemia
Common in those of African descent Hereditary disorder caused by a mutation in the haemoglobin protein, making the RBC a sickled shape and give low oxygen levels. They can block small blood vessels, leading to hypoxic damage of tissues Heterozygotes are protected against malaria parasites, so it is selected for
What are the two major bone structure types?
Compact and spongy bone
Tight junction
Completely encircles the cell, provides a seal to stop molecules moving inbetween
What type of epithelium is the germinal layer?
Complex stratified
What is the same and what is different between compact and trabecular bone
Composition is the same, but the 3D arrangement of the components is different.
Heterochromatin
Condensed DNA can't be translated
Modern micro-scale imaging
Confocal microscopy Electron microscopy
What is NOT a function of microtubules?
Connect cells together from cell junction to cell junction
Hemidesomosome
Connects the basal surface of an epithelial cell to the underlying basal lamina
Which of the following proteins is NOT involved in cell adhesion (to other cells or the extracellular matrix)?
Connexins (the ones that are = integrins and cadherins)
Steps of synaptogenesis
Contact between the cells Stabilise the contact Cell adhesion occurs Signalling occurs between cells Maturation, developing synaptic vesicles and of receptors
Brown adipose tissue cell structure
Contains cells with multiple lipid droplets, interspersed among abundant mitochondria Darker appearance
Structure of RBC
Contains haemoglobin Lacks a cell nucleus to give it more space Functional for around 100-120 days in adults (as it loses their flexibility to get through veins)
Extrinsic mechanisms
Controlled by extracellular signals between dughter cells, daughter cell and surrounding cells, or the precursor and surrounding cells
Colony Stimulating Factors (CSFs)
Controls with path the descendant of a HSC They have the ability to stimulate the growth and differentiate progenitor cells into colonies containing different blood cell types
4 main domains of NCC
Cranial Cardiac Vagal Sacral
Vasculogenesis
Creation of blood vessels, starting in the blood islands of the yolk sac It occurs within each organ as it develops Vessels do NOT arise from existing blood messels
What does the vacuole do?
Critical for osmotic pressure (acting against the sheath) that gives the notochord its rod-like appearance. Pressure also provides properties that support embryonic elongation
Issues of synaptic signalling
Critical for signalling in the nervous system Results in issues in memory, autism spectrum, and mental health disorders
Outer layer of egg
Cumulus layer (technically not a layer)
treatment of cartilage
Currently, limited repair capabilities as there is no blood supply But stem cell could be very useful in the future
G1/S phase control
Cyclin D binds to CDK4, resulting in the transcription of genes including cyclin E Cyclin E prepares the cell for S phase The levels of TFs that promote the expression of the S-phase cyclins and DNA synthesis enzymes increase Levels of the molecules involved in inhibition of entry into S phase are decreased
Surface specialisations of epithelial cells
Cytoskeletal components that push through the plasma membrane
Cell lineages of the trophoblasts
Cytotrophoblast Synctiotrophoblast Extravillous trophoblast (EVT)
What is responsible for attaching the placenta to the uterine wall
Cytotrophoblasts
Intracellular signals that can cause apoptosis
DNA damage, changes in intracellular calcium
Euchromatin
DNA is less condensed, more open and accessible
Synthesis (S) phase
DNA is replicated Replication begins at many sites along the length of the chromosome It is checked for any incorrect copying
Heterochromatin
Dark regions Tightly packed DNA, indicative of transcriptionally INACTIVE regions of DNA Nothing can access this part of the DNA to switch on these genes
Histology of bone
Darker coloured pink is older bone, bone that has been more thoroughly mineralised Lighter coloured pink is bone that has just been deposited
Describe fertilisation and implantation in humans (day 0 to day 8)
Day 0 - Fertilisation occurs Day 1 - First cleavage Day 2 - 2 Cell stage Day 3-4 - 4 Cell stage then 8-cell uncompacted morula Day 4 - 8-cell compacted morula Day 5 - Early Blastocyst - Trophectoderm Day 6-7 - Zona Pellucida - Late Blastocyst Day 8-9 - Implantation of Blastocyst - Epiblast and Hypoblast
When are germ layers formed?
Day 6 -19
Implanted blastocyst occurs at what day?
Day 8-9
When is implantation of the blastocyst?
Day 9 Before this, cell is just swimming around
Neutrophils
Defence against invasion by microorganisms, especially bacteria Only lasts 6-7 hours in blood, 1-4 days in connective tissue They are very active phagocytes
Neutrophils
Defence against microorganisms (esp. bacteria)
Eosinophils
Defence against parasites and protozoa Stained by eosin
Resolution
Defined as the ability to distinguish two very small and closely-spaced objects as separate entities
An siRNA is designed to target the signalling protein Fgf8. This is injected into a Xenopus embryo at the single cell stage. What is the likely effect of this manipulation?
Degradation of Fgf8 mRNA, leading to much less Fgf8 protein being produced (knockdown). This may inhibit gastrulation
What is the RBC function?
Delivers oxygen to body tissues, done through the strong binding of oxygen to the haemoglobin Haemoglobin also binds to carbon monoxide
Parts of a neuron
Dendrites Cell body Axon Axon terminals Synapse
Compact bone
Dense and solid Diaphysis of long bones
Best type of connective tissue for strength in many directions
Dense, irregular
Best type of connective tissue for strength in one direction and flexibility
Dense, regular (e.g. bones, tendons)
Compact bone
Dense, solid bone
Vagal and sacral NCCs
Derivatives include the parasympathetic ganglia (gut associated neuronal cells) Important for peristaltic movements of the bowel
Osteoclasts
Derived from haematopoietic stem cells (different lineage from the other bone cells) They are large, multi-nucleated phagocytic cells (like a macrophage) Responsible for the breakdown and resorption of bone Secret acids and enzymes that digest the bone matrix
Osteoblasts
Derived from osteoprogenitor cells Responsible for the formation of new bone Secret organic components of bone matrix
What is the acrosome derived from ?
Derived from the Golgi
Acrosome reaction
Derived from the Golgi apparatus, contains digestive enzymes The enzymes are needed to break through the layer of cumulus cells that surround the egg
Dermatome forms..
Dermis of the back
Cell fate
Describes what cells will normally develop into
Name and role of filaments in muscle cell
Desmin filaments Provide key strucutral support, connecting the sacromeres to the cytoskeleto
Notch signalling
Determines the placement of somite formation
Fate mapping is a technique that
Determines what tissue cells normally form
Gonadal devlopment
Develop from the genital ridge. Sex determination occurs at about 40-44 days, before that they are set up with reproductive system that can form both
Development is considered ___? When do fate of cells become determined?
Development is progressive and the fate of cells becomes determined at different times in different tissues.
Hematopoiesis
Development of blood cells
Differentiation
Development of specialised cell types
Tumours of the male germline
Development of testicular cancer happens early in development due to an issue. Cancer doesn't start to grow until puberty, mid 20s.
What is the developmental pathway of cardiac muscle?
Develops from lateral mesoderm
What did Nusslein-Volhard and Wieschaus do that won the Nobel Prize?
Did a large scale genetic screen of patterning genes. Identified maternal-effect genes, segmentation genes and homeotic genes.
Example of repulsive adhesive cue (in retinal ganglion neurons)
Different level of expression of Ephrin (Eph) receptors across the retina The gradient of Ephrin ligand in target site creates retinotopic map
Osteocytes
Differentiate from osteoblasts Responsible for bone maintenance They regulate the mineral/protein composition of bone matrix
Fate
Differentiation is a progressive process that eventually results in a commitment to a certain fate
Preeclampsia
Disease of pregnancy, unique to humans. It is likely initiated by immune dysfunction Characterised by hypertension and proteinurea after 20 weeks Only cured by delivery of placenta - cause is likely abnormal placentation Impaired artery remodelling and placental dysfunction leads to circulating toxins, resulting in hypertension and proteinuria.
Environmental cues for axons
Divided into repulsive or attractive Can be long and short range e.g. a long range repellent produces chemicals that repels the neuron, so it moves away.
Describe early xenopus development
Divides but cells stays the exact same size, not a lot of cell movemnet
Intermediate filaments
Do NOT have a unique structural basis They are made of homo- or heterodimers from a large variety of different monomeric proteins Forms a rope life structure
Allogeneic bone marrow transplant.
Donor stem cells that are a genetic match are used for transplantation.
Cardiac muscle has function in testis formation bc?
Drives blood flow to the testes
Describe Gap 2 (G2) Phase
During G2 phase, the cell prepares its by synthesizing components to ensure the survival and functionality of each daughter cell Almost like a final check
When is the uterine cycle most thickened?
During the secretory phase This is because if a blastocyst does implant, it needs to be thick enough
Dense connective tissue
ECM are densely packed collagen fibres with sparse cells Have fibroblasts Two types: dense irregular and dense regular
Differential gene expression
Each cell contains essentially the same amount of DNA but only uses a small subset of these genes
Long bone anatomy
Each end is the epihysis Shaft is the diaphysis In the middle there is medullary cavity
Chick research focus
Early embryonic development Body patterning Reproductive biology
Homunculus
Early theory of hereditary Gametes contained a complete preformed individual, and gets bigger Any maternal characteristics are attributed to egg and gestation 'Man the seed, woman the incubator'
Cells that remain in the epiblast layer during gastrulation become the...
Ectoderm
From which germ layer are neural crest cells derived?
Ectoderm
Which germ layer does the nervous system develop from?
Ectoderm
What is the origin of neural crest cells (NCCs)
Ectoderm Neural crest forms at the juxtaposition of the non-neural and the neural ectoderm
Three germ layers
Ectoderm Endoderm Mesoderm
Development of nervous system
Ectoderm forms neural plate Becomes CNS neurons and glia Forms brain, spinal cord, retina and neural piruitary Neural crest gives rise to PNS and other tissues
These targets are generally _______, which do what?
Effector proteins which implement the appropriate change of cell behaviour
Why are we made up of individual cells?
Efficiency (as SA increases, better for nutrient/oxygen supply and waste disposal) Specialisation (numerous small cells allow for specialisation)
Cleavage divisions
Egg gets divided into a number of small cells
Cleavage divisions
Egg stays the same size, but divides into a number of smaller cell Not a lot of cell movement
What happens in the acrosome reaction?
Egg's cumulus layer is breached by acrosomal enzymes, so sperm head can reach the egg surface Acrosome contents help sperm head break through Sperm fuses with egg, contents of sperm enters the egg
Notochord
Elongates anterior to posterior, contributing vertebral column. Located ventral to the neural tube
How did the study of developmental biology originate?
Embryology (descriptive study of embryonic development), cytology (study of cellular structure and function) and genetics
Describe Embryonic SCs and how its derived
Embryonic SCs are isolated from inner cell mass of blastocyst OR primordial germ mass of fetus Can form all 3 germ layers and are pluripotent
Mesenchyme
Embryonic connective tissue - gives rise to most of the body's connective tissues, bones, lymphatic and circulatory systems It is comprised of the extracellular matrix Cells of the mesenchryme are able to migrate through this tissue, allowind development of structures
What is required for a mouse knock out?
Embryonic stem cells Host blastocyst DNA construct with drug (antibiotic) resistance gene for selection DNA construct containing sequences of the gene you are targeting in the knockout
What kind of cell-cell communication is testes-testosterone production?
Endocrine communication
Cells that move through the primitive streak to displace the hypoblast become the...
Endoderm (definitive)
Allantois
Endodermally derived and lines ventral outpocketing of the hindgut
Allantois
Endodermally lined ventral out-pocketing of the hindgut In other vertebrates it is the major respiratory organ and repository for urinary wastes For mammals, it is used for respiration.
Non-receptive, early secretory phase of the blastocyst-uterine
Endomertrial lumen is not ready for blastocyst to attach
What lines the lumen of the endometrium?
Endometrial epithelial cells
Decidulisation
Endometrial stromal cell undergoes decidualisation, where the cells change shape and become highly secretory It promotes the invasion of trophoblasts
Three layers of the uterine wall
Endometrium Myometrium Perimetrium
Blastocyst implantation
Endometrium must be receptive Blastocyst apposes the uterine luminal epithelium Trophoblast differentiates into the trophectoderm, which invades between epithelial cells to form placenta
Function of endometrium in menstrual cycle?
Endometrium senses Prog hormone withdrawal that occurs from Corpus luteum regression. Withdrawal of prog, feeds back to endometrium, and no longer supports thickening or high rate of proliferation to sustain the thick level of endometriual build up. and layer is shed at menses
Risk factors for ectopic pregnancy
Endometrosis, IVF, smoking, chlamydia
How does angiogenesis occur?
Endothelial cell contacts loosen, with ECM breaking down at specific points These exposed endothelial cells will then proliferate, and form new vessels Loosened cell-cell contacts may allow the fusion of capillaries to form wider vessels such as arteries and veins
Spiral artery remodelling
Endovascular extravillous trophoblast and immune cells destroy endothelial and smooth muscle cells They re-line them by producing and embedding themselves in fibrinoid It increases the diameter Reduces artery resistance and increases blood flow This means that it is not a constant blood flow but a slow trickle of blood. High blood flow can be really damaging to villi.
Major functions of white adipocyte
Energy storage Can secrete hormones (endocrine) It is UCP1 negative
Monocytes
Engulf and destroy bacteria Present antigens to T lymphocytes
What is the skeleton of sharks and rays made up of?
Entirely of cartilage
2 ways that stem cells produce daughters of different fates
Environmental asymmetry Divisional asymmetry
Immunohistochemistry
Enzyme tag to the antibody instead of a fluroescent marker. When you add the appropriate chemical substrate, the enzyme produces a coloured product Where the signal is detected and how much shows how much protein is present
Describe the process of capacitation
Enzymes secreted by the uterine wall which: - Generate an influx of Ca2+ which increases sperm motility and makes sperm hyperactive - Alters the plasma membrane of the sperm head to facilitate binding to the egg
Endothelial cells that give rise to veins express...
EphB4 - the Ephrin-B2 receptor
Endothelial cells that give rise to arteries express...
Ephrin-B2 membrane bound ligand
Upper (dorsal) layer of inner cell mass
Epiblast
What is the source of all germ layers, which will then give rise to all tissues and organs in the embryo?
Epiblast
Epiblast
Epiblast divides into two layers - The amnion forms the protective layer around the embryo - The embryonic epiblast undergoes gastrulation - trilaminar
What does myotome divide into?
Epimere and hypomere They are specific types of muscle
Describe the epithelial-mesenchymal relationship
Epithelial cells have been shown to possess the capacity of changing into mobile mesenchymal cells - "epithelial to mesenchymal transition" - critical for embryogenesis (and a disaster in cancers!
Collective cell migration
Essential for building, shaping and remodelling tissues BUT it contributes to cancer progression
Pattern formation
Establishment of body plan, axes Where germ layers are specified Abnormalities are usually seen here, but when you can see it that means it probably happened earlier so need to look at the step before
Pattern formation
Establishment of body plan, axes Specification of germ layers
Follicular phase hormone
Estrogen It peaks just before ovulation and the receptive stage
Example of collagen structure
Example: Tendon - 90% collagen - Tensile strength is huge - Muscle is 5kg/cm2
Transplantation experiment
Experiment where one part of the embryo is removed and replaced with another part from a DIFFERENT embryo
Recombination experiment
Experiment where one part of the embryo is removed and replaced with another part from the SAME embryo
Amniotic membrane
Extra-embryonic ectodermal cells lined with nonvascularised extra-embryonic mesoderm
Name 2 extracellular and intracellular signals that trigger apoptosis
Extracellular Signals - Toxins, hormones, growth factors, nitric oxide, heat, radiation, nutrient deprivation, hypoxia - these signals activate or inhibit apoptosis Intracellular Signals - DNA damage, changes in intracellular calcium
ECM
Extracellular matrix Consists of cells separated by varying amounts of extracellular substance The proportion of cells is in the minority
Plasma
Extracellular matrix of the blood system It is around half of the blood content Transports nutrients, metabolic residues and hormones
Signalling pathway components and principles
Extracellular signalling molecules Receptors Intracellular signalling pathways Effector proteins
How are epithelium bound together?
Extraceullar junctions
Amniotic membrane
Extraembryonic ectodermal cell derived lining with nonvascualized extraembryonic mesoderm (tiny little BVs)
Secondary yolk sac
Extraembryonic mesoderm undergoes a separation, then closes to isolate an area of the yolk sac
Master regulator in Drosophila example
Eyeless (ey) It is present as a TF in mouse and humans, and when mutated leads to eye defects. But in Drosophila, it is a master regulator and will causes it to be eyeless
Eyeless mutation
Eyeless expression in the furrow leads to the eventual activation of some 2000 genes needed to form an eye. Eye is a homeobox gene If the eyeless gene is expressed in different places, you can create eye development in different places (e.g. legs). This is because eyeless is a master control gene.
What is the key ligand in development of hemangioblast?
FGF2 BMP (Develops from mesodermal cells)
Molecular basis of left-right asymmetry
Factors (FGF-8 and Shh) secreted by node, then the cilia direct the flow leftward They induce a cascade of events in the left side
Ig superfamily
Family of proteins with heterophilic attachments to - integrin ligands - other Ig proteins of the different type - Ig proteins of the same type
Long range cues
Far away, based on chemicals released by diffusion that the cells detects
Two blocks of polyspermy
Fast - electrical potential of membrane changes, blocking sperm from entering Slow - cortical granules fuse, hardening vitelline envelope
Give examples of 2 loose connective tissues Derived from?
Fat and blood derived from mesoderm
Method 2 - genetic and cellular markers Fate mapping give an example
Fate mapping can be seen in an example such as transplantation of quail cells into a chick host Fate maps can be generated using cell marking approaches
What occurs once the sperm enters the egg?
Female pronucleus completes second meiotic division Unification/syngamy Polar body directs cleavage pole Sperm centriole directs formation of chromosomes along the mitotic spindle
Placental immunology
Fetus is semi-allograft
What makes up the ECM?
Fibres and ground substances
Example of reticular fibre
Fibres surround individual sheets of liver cells Fine, open meshwork of fibres facilitates exchange of substances between hepatocytes and blood
Major cells that make up connective tissues
Fibroblasts Chondrocytes Osteoblasts Adipocytes
Types of ECM
Fibrous proteins (mostly collagens) Proteoglycans and glycosaminoglycans Glycoproteins
What are the roles of evidence?
Find it, lose it, move it - Correlative evidence (is the molecule or process there) - Functional evidence (just because its there doesn't mean it is doing something, lose it) - Progression of evidence (change the process or molecule, see if it can direct a dev event
E-cadherin
First cadherin to be expressed in development (at 2 cell stage and on)
Cleavage stages of the human embryo
First cleavage gives rise two 2 cells, called blastomeres. Day 2 has four blastomeres Day 3 or 4 has eight blastomeres Day 5, embryo called a blastocyst and blastomeres form inner cell mass
Gap 1 (G1) Phase
First part of interphase, the longest Cell functions normally Protein and organelle synthesis occurs such that the cell doubles in size
Difference between cillia and flagella
Flagella is longer and there are fewer of them compared to cilia
What is the notochord?
Flexible rodlike structure In vertebrates, the main longitudinal structural elements It serves as the axial skeleton of the embryo until other elements form (e.g vertebrae) form. Gives structure in early development In later vertebrate development, it becomes part of the vertebral column, cushioning it so bone does not grind on bone.
The neural tube then becomes what in adulthood?
Fluid filled space in neural tube continues into adulthood to become the ventricles in the brain - contains cerebrospinal fluid
Plasma membrane
Fluid mosaic Incorporates receptors that allow the cell to respond to signals from outside Selectively permeable
Three major components of connective tissue
Fluid or ground state component Fibres Cells
When does capacitation of the sperm occur?
Following exposure to enzymes secreted by the uterine wall This is done so the sperm can penetrate and fertilise an egg
Why are we made up of individual cells?
For efficiency and specialisation
Why do we have different types of asymmetrical cell division?
For production of neurons and maintenance of progenitors
Why are sheep used as models sometimes?
For size similarity - used for things like foetal physiology, foetal respiratory, kidney development
Removing a somite with some notochord tissue or removing a ventral neural tube
Form cartilage Shows they communicate with each other
Germ cell production
Formation byy spermatozoa is through repeated cell divisions, meiosis and morphogenic changes There is a very high rate of cell date during spermatogensis - so that the best sperm cells possible are selected
Clock and wavefront model
Formation of somites, the wave of developmental signals causes the periodic formation of new somites
What is considered to be the first sign of gastrulation?
Formation of the primitive streak
What is the beginning of gastrulation?
Formation of the primitive streak
Hypoblast
Formed from lower (ventral) layer of the inner cell mass
Paraxial mesoderm
Forms in to cylinder shaped segments and elongates As primitive streak regresses, the paraxial mesoderm buds off into somitomeres (and then somites) What happens to the somites depends on its location on the axis
The paraxial mesoderm forms into what? and what is it near?
Forms into characteristic cylinder-shaped segments. In the immediate vicinity of the neural tube and the notochord
Osteoblasts
Forms new bone Derived from osteoprogenitor
WHERE does paraxail mesoderm form?
Forms on both sides of the median line
Hypoblast
Forms primitive endoderm that lines the yolk sack Gives rise to extra-embryonic
Epithelial relationship with testis
Forms the germinal epithelium Tight junction connections between the germ cells and the Sertoli cells It is complex stratified, the most complex epithelium of them all
Somatic mesoderm
Forms the lateral and ventral walls of the embryo
Q: Using ENU to induce mutations in the genome and screen for developmental phenotypes is an example of reverse or forward genetics?
Forward genetics As for reverse, need to know what the gene is first
Using ENU to induce mutations in the genome and screen for developmental phenotypes is an example of
Forward genetics Because we don't know what the gene is.
Transiional epithelium
Found exclusionary in urinary tract It transitions form fat, columnar, cumboidal cells when the bladder or uretha is relaxed Then transitiosn to be flat when the bladder is full - contracted
Elastic cartilage
Found in external ear, auditor tube, larynx
Hensen's node
Found in the chicken (just called the node in humans)
The primitive streak
Found on the surface of the epiblast The streak is vaguely defined initially, but is then clearly visible as a narrow groove Head end of the streak, the primitive node, consists of a slightly elevated area
Elastic fibres
Found where tissue can be stretch (e.g. ear cartilage) Individual microfibrils are embedded in the matrix (matrix is 90% of the fibre)
What do triglycerides become?
Free fatty acids and glycerol
How quickly do somites form in humans?
From Day 25, 3-4 somites are formed per day 42-44 somite pairs are formed but some are only transient so we end up with 35-37
Where do epithelial cells come from?
From any of the three germ layers
When does human gastrulation occur?
From day 8-15
Noradrenaline
From nerve endings stimulates the cyclic AMP system, activating hormones which hydrolyse the stored triglycerides
Beta-actin
Front of moving cells
Model system examples
Fruit fly Nematodes Frogs Chicken Mouse Zebrafish
The endometrium is made up of what parts?
Functionalis layer Endometrial epithelial cells Endometrial stromal cells myometrium Spiral arteries
Asherman Syndrome
Functionalis layer doesn't become thick enough (less than 5mm) then wont provide the right nutritional environment and implantation cannot occur
Cell cycle sequence
G1 S G2 M Several checkpoints exist that determine whether cells continue through the cycle or enter apoptosis
Endoderm epithelial cells
GI tract, respiratory tract
Mesenchymal to epithelial transformation
Gain of cell adhesion
Cell aggregation
Gain of cell-cell adhesion
Progression of evidence
Gain of function. Can the process or molecule direct a development event?
Reverse genetics
Gene to phenotype Use gene to identify phenotype - analysis of developmental consequences
Asymmetric division type I
Generates another apical progenitor and a neuroblast
Brown fat
Generates heat, has high mitochondrial density
Thermogenesis
Generation of heat
Gliogenesis
Generation of new glia Follows neurogenesis
Erythrocytes involvement in testis
Generation of the vascular Testicular torsion
Homeotic genes
Genes that determine basic features of where a body part is. If mutated, inappropriate form for a given segmentation level
Segmentation genes
Genes that determine the number and polarity of body segments.
Haemophilia
Genetic disease affecting the ability of the blood to clot
What is the common source of gonadal development
Genital ridge
Sertoli cells
Germ cell "nurse" cells They express SRY and are involved in sex determination Produce AMH in early stages of fetal life, involved in hormone regulation Forms the blood-testis barrier and protects spermatozoon cells from the immune cell
Sertoli cell
Germ cell 'nurse cells' Have a very long cytoplasm, so they can support lots of germ cells. Expresses SRY (not the germ cells)
Removing a young somite alone
Gives mesenchymal cells
Removing a somite with dorsal neural tube
Gives striated muscle
What type of protein monomer is the basis for microfilaments?
Globular actin
Extracellular matrices
Glycoproteins Proteoglycans Haluronic acid
Intermediate mesoderm fate
Goes on to form the gonads and the kidneys
Intermediate mesoderm fails to develop properly then this affects
Gonadal development
Describe how testicular cancer develops
Gonocyte arrests in germ cell differentiation, developing into carcinoma in situ (CIS) cells, then at puberty cancer will grow
Drosophila as a model organism discoveries
Good for genetics Found that genes are located on chromosmes, chromosomal inheritance specifies gender, how genetic material exchange exposure to X-rays can cause mutations Important for body patterning, stem cell biology and reproductive biology advancement
Sulci and gyri
Grooves and folds of the normal human brain
Cancer in epithelium lining
HPV infections likes immature squamous cells
Functions of bone marrow
Haemopoiesis Phagocytosis of cell debris Storage and recycling iron (Hb synthesis) Production of antibodies
What happens to the ectoderm?
Half will become nervous tissue The rest will become epidermis
Cortical lamination
Happens from radial migration Neurons migrate to form the cortex in an inside-out manner Newer/younger cells move further out. Youngest neurons are closest to the outside of the brain.
When do cells start to differ?
Hard question - Equivalence hypothesis OR - asymmetric hypothesis
Unilocular
Having one compartment or unit This is in white adipocytes - triglycerides are stored in a single locus
Possible cell lineages from embryonic stem cells
Heart cell precursor Neural precursor Blood cell precursor Lymphocyte precursor
What are some of the key features of cardiac muscle structure?
Heart muscle develops through joining together at junctions called intercalated discs They are unique to cardiac muscle
What drives the endochondral ossification?
Hedgehog signalling pathway
Microfilaments structure
Helical filamentous polymer Their helical conformation is based on two intertwined chains of G-actin monomers
What are microfilaments
Helical filamentous polymers, 7-9nm diameter, variable length
The epithelial-mesencyhmal relationship
Helps form nearly every organ in the body Mesenchymal cells can migrate esily, while epithelial cells cannot Epithelial cells can change into more mobile mesenchymal cells, critical for embryogenesis - but this is bad for cancers
Why are bones composed of both types?
Helps us withstand the different mechanical forces we are exposed to.
Primitive node name in chick
Hensen's node
Semi-dominant mutation
Heterozygote results in a deformation, while the homozygote is embryonic lethal.
Cyclopia caused by?
Hh signalling abnormality
What causes cyclocopia?
Hh signalling disruptions
Desosome
Holds two cells tightly together via their attachment to intermediate filaments in the cytoplasm
Intermediate filaments
Homo-or hetero dimers, but there are lots of monomer proteins possible Used for stability, support plasma membrane
What has occurred in the drug-resistant cells?
Homologous recombination Two DNA molecules have recombined, to incorporate the targeting DNA into the mutated chromosome
Trabecular bone
Honey comb network, lots of holes Epiphysis of long bones
Genetic approaches
How do genes control development?
Experimental approaches
How do molecules or processes causes visible changes in embryos? How do embryonic cells respond to perturbations (deviation)? How do cells order themselves into tissues and organs?
What is the overriding question of dev bio?
How does a single cell develop into a multi-cellular, functional adult?
Brain-testis molecular link
Huge overlap of human brain and testis gene expression profiles. The proteome of the cerebral cortex has 43 overlap with the testis - which is more then pretty much everything else
hCG
Human chorionic gonadotrophin Basis of urinary pregnancy tests Produced by trophoblast prior to implantation It maintains corpus luteum production of progesterone and estrogens, maintains pregnancy
What is the human and mouse chrom equivalent?
Human chromosome 21 is mouse 16 chrom equivalent
Growth factor examples
Human placental growth hormone Chorionic somatomammotrophin
Endochondral ossification
Hyaline cartilage is REPLACED with bone (does not turn into!)
Lower (ventral) layer of inner cell mass
Hypoblast
Primary yolk sac
Hypoblast proliferates and descends It joins with membranous structure to form primary yolk sac
Explain the brains role in the menstrual cycle
Hypothalamic pituitary gonadal axis - brain produces gonadotrophins FSH and LH. FSH and LH peak just prior to ovulation, regulated by surge in estrogen produced by the ovary, which feeds back to the brain to trigger ovulation
How is the Bilaminar embryo formed and what is it made up of?
ICM divides into 2 layers which form: Hypoblast and epiblast
Mitosis phases
IPMAT
What are the stages of Meiosis
IPMAT interphase prophase metaphase anaphase telophase
Factor
If there is a transfromation of lean adipose tissue to obese adipose tissue. This will result in release of chemokines which recruit macrophages Leads to free fatty acids increase, leptin increase Overall can lead to systemic insulin resistance Some things that are released by adipocytes are bad, but some are beneficial.
What if you add another notochord?
If you placed Shh ectopically lateral to the neural tube instead of ventrally It will induce a second set of motor neurons and another floor plant Shows how vital Shh is
Electron microscope images
Imaging internal structures within cells with high resolution Especially good for looking at organelles
Angioblast
Immature vessel cell Develop from haemangioblasts
What is one of the most severe limiting factors in stem cell therapy?
Immune rejection Cells from a genetically different individual are likely to be rejected as foreign
Cranial NCCs
Important cranial NCC derivatives include (of the face) = cartilage, bone, connective tissue. They form borns through intramembranous ossification
Contact dependent signalling
Important for asymmetric cell division, inhibiting neural differentiation Laterla inhibition is via the Notch signalling pathway and is critical for this process Binding of the Notch receptor results in transfer of part of the receptor to the nucleus where it blocks the expression of neural genes
Dartos muscle
Important for temperature regulation, produces the wrinkled surface of the testis
Why are junctions important?
Important in maintaining adult tissues, development of tissues
Trunk NCCs
Important trunk NCC derivatives include sympathetic ganglia, Schwann cells, adrenal gland medulla, pigmented cells of the skin
Compare gamete formation in males and females
In females - Meiosis begins during embryogenesis, and arrests at prophase 1 (meiosis 1) - Meiosis reinitiated at puberty in specific oocytes that begin to mature, and then arrests at metaphase II (meiosis II) - Meiosis not completed in oocyte until fertilisation occurs In males - Meiosis begins at puberty and doesnt stop
Distribution of brown and beige fat
In human adults, mainly found in the neck and collarbone area, and some paravertebral. It is more dispersed - more beige. In infants, found in the back - much more localised.
Recessive trait
In most instances a phenotype is only observable in the homozygote Mice when the function of the gene is completely lost.
Where are heterochromatin and euchromatn found?
In non-dividing cells, as the chromatin is not formed into chromosomes
Dominant Trait
In some instances a phenotype is observable in the heterozygote mice when gene function is partially lost. In some instances a complete loss of the gene will result in embryonic lethality. Embryos at different developmental stages throughout gestation are analysed and genotyped to determine the time point at which lethality has occurred.
What happens when the blastomeres are separated in a 2 cell human embryp?
In some species, this will result in the death of the embryo (e.g. c elegans). But for mammalian embryos, each blastomere can form an individual zygote and result in twins. Can do this up to the 8 cell stage. Early in development is very regulative
Where is blood produced?
In the embryo, by many different tissues (yolk sac, liver, spleen). In the adult, in the bone marrow This is because there are no bones in an early embryo
Where does spermatogenesis occur?
In the seminiferous tubules of the testie
Does the notochord last past development?
In vertebrates - no. It is only a transient structure. In lower types of chordates and in primitive fish, the notochord persists into adulthood.
Growth
Increase in body size
If there is more osteoblast activity then osteoclast activity..
Increase in bone mass Forming more bone matrix then we are resolving
What happens when there is lower myostatin function?
Increase in muscle mass (found in bull, a boy) Myostatin is still there, but not as functional This could be useful to stop individuals (due to health issues) having a loss in muscle mass
What is the function of remodelling of the uterine spiral arteries?
Increase the diameter and reduce pulsatile contraction of the arteries
Hypercoagulable states
Increased risk for blood clots developing in the arteries and veins They can travel through bloodstream, cause deep vein thrombosis or a pulmonary embulous
Slow responses
Increases in cell growth and division Changes in gene expression
Why is the RBC biconcave?
Increases surface area, allowing better efficiency for molecules coming in and out Also helps with flexibility
Chick research advantages
Incubation period of only 21 days Human and chicks have highly similar stages of development, the fundamentals of early embryogenesis is learned from the chick
Endochondroal ossification
Initial chondroification It follows the initial patterning of the cartilage deposition - cartilage growth is primarily a maturation-based process
How do you make a transgenic animal?
Inject gene into pronucleus of a fertilised egg Then transfer the zygote into a house mouse Transgenic mouse will be born
Where are ES cells from?
Inner cell mass of the blastocyst
What controls neural migration?
Inside out lamination
Caudal dysgenesis
Insufficient mesoderm during gastrulation Issues with formation of lower limbs Sirenomelia - aka Mermaid syndrome
Down syndrome symptoms noted
Intellectual disability Condition was congenital (present from birth) Specific facial features (slanted eyes, flat nose, enlarged tongue) Short life expectancy
What controls the fate of the epithelia?
Interaction with mesenchyme
Where is the urogenital system derived from?
Intermediate lesoderm
The urogenital system is derived from?
Intermediate mesoderm
Identify and describe the stages of mitosis
Interphase - Chromosomes decondensed, and in active transcriptional state Prophase(early) - Chromatin begins to condense to form chromosomes Prophase(late) - Nuclear envelope disappears - spindle apparatus forms Metaphase - The spindle grows and forms attachments to chromsomes and move to equatorial plane. Can be stained and show banding patterns Anaphase - Centromeres divide to create chromosomes - seperates cell Telophase - Nuclear envelope assembles - Furrow appears to create 2 cells
Fibrocartilage
Intervertebral discs Transitional between dense connective tissue and hyaline cartilage Tough and resists compression Chondroctyes or single or in pairs
What happens when Snai1 is knocked out?
Intestinal stem cells are lost from the crypt base
How do the spinal nerves divide?
Into dorsal and ventral rami They supply each division of the myotome
Gap junctions
Intracellular channels, allow changes in membrane potential
Strong attachments of epithelial cells
Intracellular junctions Can be on the cells lateral surface, or on the cells basal surface
The binding activates the receptors, which in turn activates one or more ___________ which? (2 things)
Intracellular signalling pathways Which: - process the signal inside the cell - distribute the signal to the appropriate intracellular targets
Cavity that is surrounded by lateral plate mesoderm
Intraembryonic coelom (cavity)
How does embryonic circulation work?
Intraembryonic vitelline link to yolk sac, umbilical vessels link to the pacenta. This allows primary erythrocytes to begin to circulate throughout the embryo. They are found in the human bloodstream, just before the heart tube begins to beat (22 days of gestation)
Two forms of ossification
Intremembranous Endochondral
What determines migration pathway?
Intrinsic properties (things in the cell). e.g. adhesion molecules (amount of them change as cell migrates to final destination) External environment e.g. extracellular matrix
Flagella
Involved in cellular movement, and movement of materials along the outside of the cell
Flagella
Involved in cellular movement, and moving materials along the outside of the cell E.g. sperm tail
Splanchnic mesoderm
Involved in formation of the wall of the digestive tract
Describe what gastrulation is and what it forms
Is a phase in the embryonic development in most animals. Consists of a complex and coordinated series of cellular movements which occurs at cleave It forms the 3 embryonic germ layers: Ectoderm - Epidermis, lens retina, internal ear, CNS, middle and posterior pituitary and pineal gland Mesoderm - Muscles, connective tissue, dermis circulatory system, kidney, gonads and uterus Endoderm - Midgut, bladder, lungs, liver, thyroid, anterior pituitary
Correlative evidence
Is a process or molecule present at the right time to direct a developmental event?
Mesoderm in the somite
Is influenced from the surrounding tissues Neural tube can direct the development of skeletal muscle All of the different things (nueral tube, somite, notochord) are all communicating with each other to make sure they are in the right place
Issues in synaptic signalling can cause?
Issues in signalling: memory, autism spectrum, and mental health disorders
Advantage to indirect immf
It amplifies the signal as two of the secondary antibody can bind to the one
In higher vertebrates, what does the notochord become?And notochord cells?
It becomes ossified in regions of forming vertebrae (invertebral discs), and notochord cells form the centre of these discs, called nuclei pulposi which cushion the vertebrae
When does meiosis first commence for females?
It begins meiosis very early on, but stops at prophase I until puberty
If p53 is not functional..
It cannot stop the cell cycle
When Rb is inactivated...
It cannot stop the cell cycle
What happens to the sperm centriole after fertilisation?
It duplicates, and forms the first mitotic spindle (very important). Allows it to undergo the first division
Epithelium cell junctions
It forms sheets of cells, serve as a barrier (selectively permeable) Strong attachments between cells - intracellular junctions
Placental surface area
It has a large surface area due to microvili on surface. This is so it can transfer things from fetus to mother and vice versa. This means that toxins can pass through though
Placental structure
It has a large surface area, with a continuous layer of multinucleated cells. Microvilli are bathed in maternal blood Has epithelial plates, which are extremely thin barriers
Ts65Dn ouse model
It has altered craniofacial development, memory and learning deficits, age-related alterations in the forebrain It carries 132 genes that are syntenic with human Chromosome 21.
Describe lipid droplet size and proportion of Beige adipose tissue
It has greater variability in lipid droplet size and a greater proportion of lipid droplets to mitochondria giving it a brown appearance
Why do epithelial cells sit on a basal lamina?
It helps with cell adhesion, orientation and shape Normal epithelial cells never cross the basal lamina
What controls the composition of the ECM?
It is according to the function of tissue ECM is usually mae by the cells wihin it All connective tissue within the body is continuous with all other connective tissue
Components of plasma
It is around 90% water Contains plasma proteins, inorganic salts, amino acids, vitamins, hormones etc. (Don't need to know in specific detail)
Why is BAT brown?
It is due to the numerous mitochondria, and the large number of blood capillaries
FGF8
It is expressed in the primitive streak, is important for migration of mesodermal cells Disruption of FGF8 (targeted) stops cell migration in gastrulating mouse embryo
Muscle growth regulation
It is negatively regulated Myostatin stops muscle growth when muscle has reached its normal size
Histology of smooth muscle
It is single, fusiform Only one nucleus, centrally placed There are NO striations
How tight is the regulation of somitogenesis?
It is so tightly controlled can use this to work out what day of development they are. Counting the somites defines the embryonic age - so if you don't know when the mating occurred or if the development has been a bit slower.
Transcription factors and haematopoiesis
It is the combination of TFs that is responsible for specific pattern of gene expression - leads to a specific type of differentiated cell
Why are epithelial cells orientated/polarised?
It means that they can form surfaces and tubes, means that they are highly arranged
Capacitation of sperm
It primes the sperm for penetrating the egg Happens in the female, through enzymes secreted by the uterine wall Makes the sperm hyperactive (through Ca influx), and alters the plasma membrane of the sperm head to facilitate binding to the egg
Repair of smooth muscle
It retains the ability to regenerate and multiply quite well It is highly versatile
Why is cell migration important?
It underlies tissue formation during embryonic development, wound healing and immune responses in the adult It is essential for - gastrulation - neural crest migration - germ cell migration
Protein found for intermediate filaments of the skin
Keratin
What provides key structural support in skin
Keratin filaments
Name and role of filaments in epithelial cell
Keratin filaments Provide skin with strength and waterproofing
Sonic hedgehog (Shh)
Key for nervous system, limb bud, gut and carniofacial structures
Induced Pluripotent stem cells
Key transcription factors can transform a somatic cell into a pluripotent iPS cell It avoids ethical concerns as comes from patient Differentiates the cell into the affected cell type, and can transplant healthy cells into the patient. Or you can reproduce the disease-specific phenotype in the cell, and assay multiple drug screens. Then use the results to treat multiple patients.
Tetra-amelia
Lack of all four limbs, carniofacial, urogenital defects
What triggers menstruation?
Lack of progesterone Can't sustain the thick layer of the secretory phase So it sheds a layer
Duchenne muscular dystrpphy
Lacking from muscle fibres Absense of dystrophin makes muscle fibres more susceptibel to damage when physically stressed
Lamellae in compact bone
Lamalle are arranged into osteons (Haversian systems) Lamellae form a series of rings surrounding a central canal, organised around a blood vessel
Fast twitch fibres / Type II
Larger fibres, Type IIa = fast oxidative where there are lots of mitochondria, undergo anaerobic glycolysis, generate high peak muscle tension. Middle distance swimmers, 400 and 800 runners Type IIb = fast glycolytic has less mitochondria and myoglobin but stores lots of glycogen, fatigues rapidly but has rapid contraction. Sprinters, weight lifters
When was the cause of Down syndrome found?
Late 1950s French researchers found the cause was Trisomy 21
Lateral plate mesoderm comes from..
Lateral plate mesoderm (becomes splanchnic then develops on)
Where are blood cells derived from (germ layer)?
Lateral plate mesoderm - the splanchnic
Where is cardiac muscle derived from?
Lateral plate mesoderm, splanchnic
How does intermediate mesoderm form?
Laterally
What protein conserves node monocilia proteins? What animals is it found it?
Left-Right Dynein (LRD) mouse, chick, frog and zebra fish
Leukaemia and cancer, and Down syndrome
Leukemia is significantly more common in DS. It is a clonal population of undifferentiated progenitors in the blood.
Stem cells are marked with?
Lgr5
Micro-scale imaging
Light microscopes Doesn't have high resolution, but still can see quite a bit
Euchromatin
Light regions Loose, open chromatin Allows ACTIVE transcription and therefore gene expression
Ependylmal cells
Line ventricles
Yolk sac
Lined by extra-embryonic endoderm It birds and reptile it provides nutrition In mammals, blood cell development occurs there
Mesoderm epithelial cells
Linings of the inner body cavities (e.g. circulatory system)
Adipocytes relationship with the testis
Lipids are required for hormone biosynthesis Male adiposity has a significant impact on fertility Testosterone impacts adipocyte proliferation, differentiation and fat distribution
Signalling Centre
Localised region of the embryo that can influence how surrounding cells will develop.
Endocrine signalling
Long distance signalling involving hormones travelling through blood stream
Microfilaments (actin filaments)
Long, thin fibres Intertwined chains of globular actin monomers
Anatomical approaches
Looks at what parts of the embryo form different organism, comparisons we can see to different organisms, changes in tissues in birth defects
Pseudostratified epithelium
Looks like it is a multilayered epithelium, but it is not This is because the nuclei are at different layers throughout the peithelium Found in trachea and male epithelial system
Asymmetric diffusion controls:
Looping of the heart Looping of the gut Positioning of the liver and spleen Lobation in the liver All of these are symmetrical
Migration (cell adhesion)
Loss and gain of cell-matrix interactions
Epitheliam to mesenchymal transformation
Loss of cell adhesion
Complex stratified epithelium
Lots of partions in the epithelium Supports the developing germ cells, between sertoli cells Complex, multi layered epithelium
Desomosome
Macula aderens Hold cells tightly via INTERMEDIATE filaments
Filopodia
Made of actin bundle together, norm netwroks They are found on the mobile edge of migrating cells
What makes up gap junctions?
Made of six copies of transmembrane proteins called connexins
Simple columnar epithelium
Made up of a single layer of tall cells that fit closely together Part of digestive tract
Allantois in other vertebrates
Major respiratory organ and repository for urinary wastes
Three functions of microtubules
Make up the centrioles and form the spindle Form the flagella and cilia of a cell Provide pathway for intracellular movement of organelles
Endochondrol ossification
Making cartilage into bone Occurs during later foetal development Bone tissue is created from te cartilage template
What is the synctium
Male germ cells do not complete cytokinesis during spermatogenesis, as cytoplasmic bridges maintain connections - a syncytium Therefore, male haploid cells are supplied with all the products of a complete diploid genome
Chondrocytes and osteocytes from the male perspective
Male reproductive system lies both within and without the pelvis This changes from the embryonic to the adult stage
Function of chondrocytes and osteocytes in a foetal perspective
Male reproductive system lies both within and without the pelvis.
Advantages of humans as model
Many diseases, 5000 genetically based Self-reporting mutants Some good family pedigrees Genome sequence complete
Chondrocytes and osteocytes from the foetal perspective
Many regions of the foetus has undergone ossification, but there will be some cartilage.
Where do we find Type I slow twitch fibres?
Marathon runners In out back muscle
Placental exhange
Maternal and fetal blood exchange occurs across the trophoblast cell layers of the placenta
What is the % of maternal and paternal non-disjunction?
Maternal origin of non-disjunction - 88% (~75% at first meiotic division) Paternal origin of non-disjunction - 9% Mitotic (embryo) - 3%
Disrupted gastrulation
May be disrupted by genetic abnormalities and toxic insults Most are not survival, but sometimes they are
Semi-allograft
Means that the fetus is immunologically distinct from the mother, as there are both maternal and paternal antigens present
Risk indicators from ultrasound for Down syndrome
Measurement of specific growth ratios Small or no nasal bone Large ventricles Muchal fold thickness, an an abnormal right subclavian artery
Function of the uterus
Mechanical protection, nutritional support, and waste removal for the developing fetus during pregnancy
What is the function of the uterus?
Mechanical protection, nutrtional support, and removal for the developing fetus during pregnancy
Angioproteins
Mediate the interaction between endothelial cells, pericytes and smooth muscle cells
Principles of cell communication
Mediated mainly be extracellular signalling proteins Reception of signal usually requires receptor Binding activates receptors, activating intracellular signalling pathways Targets are generally effector proteins
Changes in cadherin expression
Mediates morphogenesis Leads to defects, reconstruction of skin
Where is the bone marrow in adults?
Medulary cavities of certain bones Vertebrae, ribs, pelvis, cranial bones, proximal ends of femur and humerus
Oogensis and spermatogenesis - SIMILARITIES
Meiosis Extensive morphological differentiation Incapacity of surviving for very long if fertilisation does not occur
What features do oogenesis and spermatogenesis have in common?
Meiosis Extensive morphological differentiation Incapacity of surviving for very long if fertilisation does not occur
Cardiac NCCs
Melancocytes Septum that separates the pulmonary artery from the aorta Muscular-connective tissue of pharyngeal arches
Myostatin
Member of TGF-beta family of signalling muscles
What can happen when there are errors in cell migration?
Mental retardation Vascular disease Tumor formation Metastasis
What is a key difference between mesenchymal and epithelial cells
Mesenchymal cells can migrate easily, in contrast to epithelial cells. Epithelial cells lack mobility and are organized into closely adherent sheets, are polygonal in shape, and are polarized in an apical-basal orientation
List the steps of how mesenchymal progenitor cells then turn into mature adipocytes?
Mesenchymal progenitor cells - commitment gene program - committed precursor cells - differentiation gene program - mature adipocytes
Mesenchyme
Mesenchyme is a type of animal tissue comprised of cells embedded in a mesh of proteins and fluid, called the extracellular matrix.
Intramembrous ossification
Mesencymal tissue is replaced with bone Gives rise to some craniofacial bones
Where do notochords come from?
Mesoderm
Where does muscle come from?
Mesoderm
Which germ layer gives rise to the endothelial cells?
Mesoderm
Where are most connective tissues derived from?
Mesoderm But some skeletal components of the head are derived from the neural crest cells
Cells invaginating through the primitive streak during gastrulation gives rise to what?
Mesoderm Endoderm
Where is blood derived?
Mesoderm (bone marrow in adults)
Blood islands
Mesodermal cells on day 18 form blood islands in the yolk sac Will give rise to the developing vascular system
How to mark cells in early embryo? 2 methods
Method 1: Tracer dyes or fluorescent markers can be injected into a cell or group of cells early in development. Watch where the cell/s move to in the embryo and what they develop into. Method 2: Genetic methods can also be used to trace cells
Terminal villous
Micro villi on syncytiotrophoblast increases the apical surface area of the cells for exchange
Nodal flow
Microcillia around the node generate a LEFTward flow of liquids along the side of the embryo = it determines which side is the left
If you were a neutrophil chasing a bacterium, which cytoskeletal elements would you be using for movement?
Microfilaments
Three main components of the cytoskeleton
Microtubules Microfilaments (actin filaments) Intermediate filaments
Major components of the cytoskeleton
Microtubules (cilia, spindle fibres, organelles) Microfilaments/actin (cytokinesis, under plasma membrane, muscle contraction) Intermediate filaments
Terminal villous
Microvilli on the syntiotrophoblast, which increase the apical surface area of the cells for exchange
Myometrium
Middle layer Consists of smooth muscle cells Contracts to push out foetus, also sheds endometrium layer during menstruation
Diaphysis
Middle part of bone
Mesenchymal cells
Migrate as individual cells, if provided with the proper extracellular environment
Describe primordial germ cell journey in humans: - Migration
Migration - During the 4th week of human gestation, PGCs migrate from yolk sac and into developing emryo - Extensive proliferation occurs during the journey
Function of the cytoskeleton
Migration of cells Movement of organelles Cilia and microvili movements Cell contraction Endocytosis Cell shape maintenance
Generation of the vasculature
Migration of endothelial cells from the mesoephros occur after SRY expression has commenced. It is all part of developing the testis structure. FGF, BMP and AMH drive testis development
Describe Mitosis (M) phase
Mitotic cyclin-CDK complexes are activated, and promote: - Stimulation of proteins involved in chromatin condensation - Mitotic spindle formation - Degradation of chromosomal structural proteins - Procession through the stages of mitosis
Microglial cells
Modified immune cells
Intrinsic mechanisms
Molecules are distributed asymmetrically in the progenitor and inherited by one daughter cell
What are intrinsic factors?
Molecules distribuetd asymmetrically in the progenitor and inherited by one daughter cell
What is nodal flow? and what does it determine?
Monocilia on node rotate clockwise and generate leftward flow of extraembryonic fluid - The direction of this flow determines which side will be the left, because the L/R decision is reversed when the flow direction is reversed by imposing artificial flow.
White adipose tissue cell structure
More common Cells contain one large central droplet of whitish-yellow fat in their cytoplasm More white appearance
Describe Step 2: Diagnostic tests
More sophisticated tests determine the karyotype of the foetus Blood tests primary test Amniocentesis --> Invasive Chorionic villus sampling --> Risk to foetus - these are now secondary test only
Morphogens
Morphogen is a chemical signal whose concentration caries and is involved in pattern formation Can be secreted by signalling centres
Signalling centres can secrete?
Morphogens
Do NCCs lose their potency after leaving the neural tube?
Most NCCs are still multipotent even after they have left the neural tube So this suggests that neural crest stem cells in vivo
Collagen fibres
Most abundant Tough and flexible, resistant to stretching. Incredibly strong. Tendons are 90% collagen
Heart defects in Down Syndrome
Most common physical abnormality in children with DS. They can be atrioventricular canal defects, ventricular septal defects, patent ductous arterious. Surgical intervention is often needed
X. laevis advantages
Most essential cellular and molecular mechanisms are highly conserved
When is endometrial lining thickest?
Most thickened at secretory phase
What causes neuronal cell death?
Motor neurons that have not made connections with muscle undergo apoptosis
Mouse models of Cr 21 trisomy and monosomy
Mouse Cr16 is the equivalent.
In female embryo, reproductive system
Mullerian ducts develop into Fallopian tubes, uterus, vagina Male duct degenerates
Stratified squamous epithelium
Multiple layers of flat cells Good for protection In skin, vagina, anus, cheek
Haematopoietic stem cells are:
Multipotent
Haemopoietic stem cells
Multipotent Can from neutrophil, erythrocytes, eosinophil, platelets etc. It has different progenitors, and forms different cells
Properties of NCCs
Multipotent stem cells They can differentiate into many cell types Show remarkable migration pathways through the developing embryo
Alpha-actin
Muscle cell contraction It interacts with myosin
Hypomere
Muscles of thorax, abdomen
Anamolaies of skeletal muscle
Muscular dystrophy
Myotome forms..
Musculature of the back, limbs and ribs
How can you regulate transcription?
Mutation of DNA affecting regulatory region, promoter, exon
What causes Homeotic transformation
Mutations in Homeobox genes
WNT3a
Mutations in humans can lead to tetra-amelia
Oligodendrocytes
Myelinate axons Insulates and supports the axons Gaps allow the signal to be replenished
Mitosis (M) phase
Myotin cyclin-CDK complexes are activated They promote stimulation of proteins involved in chromatin condensation, mitotic spindle formation, degrade chromsomal structure proteins and procession through the stages of mitosis
Myotomes grow in defined territories
Myotomes develop further and move into different areas of the body into their final forms They start to move into adult anatomy
What does testicular torsion result in if not treated within 12 hrs
NECROSIS! Gangrene and death of the testicle will occur
Apoptosis vs necrosis
Necrosis is induced by tissue injury, while apoptosis is programmed cell death. Apoptosis is much more regulated and is beneficial to the organism - while necrosis is almost always detrimental
What is the correct order of events in the development of the nervous system?
Neural induction, neurogenesis, neuronal migration, gliogenesis
Half the ectoderm will become what? and the other half?
Neural tissue and epidermis
What happens if the neurla tube doesn't close at the ends?
Neural tube defects Anencephaly - without a brain. Skin can't grow over the brain. Neural tissue continues to develop, but fluid becomes toxic and it degrades it. Baby doesn't survive. Spina bifida happens if it doesn't close at the bottom end.
Specialisation of mesoderm
Neural tube in middle Next to it paraxial mesoderm Then intermediate mesoderm Thin extremities of int. mesoderm form the lateral plate mesoderm
Name and role of filaments in neurons
Neurofilaments Provide structural support for axons, regulate axon diameter (NOT length)
How are axons guided to their targets?
Neurons extend a growth cone at the end of the axon Lot of similarities between axon guidance and cell migration, but the cell stays put and just the axon moves in axon guidance Evironmental cues help
How do neurons connect to each other?
Neurons extend out processes, called neurites (axon and dendrites) Dendrites and growth cone on developing axon
What is axon guidance does not happen properly?
Neurons fail to connect to their target Apoptosis of neurons, abnormal neuronal connections
What do myoblasts form?
New skeletal muscle fibres - they fuse together They are multinucleated with striations
Is smooth muscle striated?
No
Are actin filaments outside the cell?
No - it looks like they are sitting on the top but they are actually inside and are pushing up Cell surface specialisations are therefore cytoskeleton, as they are INSIDE the cell
Do signalling pathways work alone?
No - sometimes a mutation in one signalling factor results in mild effects. But when crossed with another single gene mutation in a different pathway, combination is generally lethal.
Disadvantages of humans as models
No experimental access Foetal material difficult to obtain Ethics Long generation time
What causes abnormal placentation and preclampsia?
No predictive markers or treatments Shallow artery remodelling, activation of anti-angiogenic factors
Are spermatozoa removed directly from the testes motile?
No, they undergo morphological changes to be motile
Transplation of the nodes
Node is so powerful that transplantation of the node can induce a secondary body axis
How is cardiac muscle formed?
Not by fusion, but by joining together at junctions (intercalated discs) As the heart increases in size with development, their contractile filaments disassemble to undergo mitosis
What drives ovary development?
Not just the lack of SRY, but this is very important Other factors drive this, genes promote ovarian development
Issues with studying menstruation
Not many species menstruate - mice and sheep don't which are the species usually used for reproductive studies
Notch
Notch works by lateral inhibitiron - when activated, cell is fated to form an absorptive cell cells adjacen to notch, turn off signal and express molecule delta, inactives notch pathway and goes down secretory cell lineage
Patterning the neural tube
Notochord signals the formation of the floor plate - mainly via the Hedgehog pathway
What does mesoderm further develop into?
Notochord, paraxial and lateral
Describe day 5 of cleavage
Now called a blastocyst
DS Aetiology i.e. what is it caused by?
Now understood that the trisomy occurs due to increases in meiotic disjunction that often correlates with increasing maternal age.
Prophase late
Nuclear envelope disappears, spinle appartus forms
Telophase
Nuclear envelope reforms, furrow appears around the cell that will eventually pinch the cell into two new cells
Proteins that are distributed differently in daughter cells during neurogenesis
Numb and Notch
Describe how Numb and Notch proteins are distributed
Numb close to basement membrane, notch away from it. Cell divides so one contains notch and other numb this determines stem cell vs neuroblast
Epithelial cells are characterised according to:
Number of layers (simple, stratified) Shape of the most superficial cell (squamous, cuboidal, columnar)
Orientation needed to form gyri
Oblique orientation
Why do neural tube defects occur? Give 2 examples of conditions that can occur.
Occur if the tube doesnt close at the ends o Anencephaly → If cranial (rostral) neuropore doesn't close, therefore brain doesn't properly development bc neural tissue exposed, skin doesn't grow over and skull doesn't form o Spina bifida → if the caudal (base) neuropores doesn't close. Problems with lower body development, and also brain development. Take folic acid to prevent.
Primitive (embryonic) haematopoiesis
Occurs in the yolk sac Transient phase that provides the embryo with its blood cells
Primitive haematopoiesis
Occurs in yolk sac All blood cell types are produced except WBC RBC predominate
The cleavage stage of development
Occurs prior to establishment to the body plan
How does asymmetrical cell division occur?
Occurs through intrinsic or extrinsic mechanisms
Where are epithelial cells?
On tissues that form the surfaces of the body, externally and internally Gastrointestinal system, lining of circulatory systems, renal system (kidneys), uterus, urinal system
How is the endoderm formed?
Once cells have invaginated, some displace th hypoblast, creating the embryonic endoderm
Describe receptivity = mid-secretory phase
Once stroma has differentiated and endometrial luminal epithelium becomes receptive - cytokines, chemoattractants and adhesion molecules are upregulated
Asymmetric division I of neurons
One daughter cell is the differentiated neuron, the other is an apical progenitor cell
Asymmetric division II of neurons
One daughter cell is the differentiated neuron, the other is an intermediate progenitor cell. This cell needs to divide at least once more in order to become a neuron
Seminiferous tubule
One of hundreds of tubules in each testis in which sperm develop
Transplantation experiment
One part of the embryo is removed and replaced with a part from a different embryo
Transplantation experiment
One part of the embryo is removed, and replaced with a part from a different embryo
Which genes on chromosome 21 are associated with Down syndrome?
Only a small proportion, as there expression is not properly regulated
Which of the following is a property of the epithelium shown in the histomicrograph below? (stratified squamous epithelium)
Only the bottom touches the basal lamina. Does not have a blood supply, cross sections may be hair follicles It is found in oesophagus and anal canal
Neuropores
Open ends of the neural tube These have to close over entirely to get normal development of the brain and spinal cord
What helps in forming the gyri and sulci?
Organisation the number of outer radial glial cells and process They lack an apical process Oblique orientation of outer radial glial process may support gyrus formation
Developmental origin of BAT?
Originate from myf5 precursor cells
Disorders of cartilage
Osteoarthritis Achondroplasia Spinal disc herniation Relapsing polychondritis
What controls the mineralisation of osteoid (ECM)?
Osteoblasts Does this by secreting calcium ions
What cells must be balanced for bone activity?
Osteoblasts and osteoclasts
What are the cell types in bone?
Osteocytes Osteoblasts Osteoclasts Extracellular matrix
Four specialised bone cells
Osteoprogenitor Osteoblasts Osteocyte Osteoclast
How is the mesoderm formed?
Other cells come to lie between the epiblast and newly formed endoderm which form the mesoderm
Trophectoderm
Outer blastocyst layer that invades the endometrium It differentiates into cytotrophoblast, which proliferates and invades into the decidua
Perimetrium
Outer layer of the uterus
Synctiotrophoblast
Outer surface of the villi
What factor is needed for angiogenesis?
PDGF (Platelet-derived growth factor) Needed for recruiting pericytes, that contribute to the wall of the new vessel
Synapsis
Pairing of homologous chromosomes during meiosis and crossing over Synaptonemal complex forms Swapping alleles around
Describe the development process of cartilage
Paraxial Mesoderm→ Somites → Gives rise to Sclerotome → Cartilage - Initial Endochondral ossification occurs during embryogenesis - Following initial patterning of cartilage deposition (by chondrocytes) cartilage growth is primarily Maturation-based process - Production of ECM and remodelling collagen fibres = final structure - Axial skeleton is initially deposited as cartilage - this acts then as a template for later bone formation
Where does skeletal muscle come from?
Paraxial mesoderm - myotome
Three lineages of mesencymal cells that give rise to bone tissue
Paraxial mesoderm = axial skeleton (vertebral column, ribs, sternum) Lateral plate mesoderm = appendicular skeleton (limb bones) Neural crest cells = Craniofacial bones (but only some, some come from paraxial mesoderm(
Optical projection tomography (OPT)
Passes visible light through an embryo - which has been rendered semi-transparent by chemical treatment It records how much light passes through, so darker regions are thicker. Looks at a particular protein A 3D embryo model is produced
Autologous bone marrow transplant.
Patients own cells (ex vivo) are used to repopulate the bone marrow.
How is the brain different to the spinal cord?
Patterning of neural tube through signalling Signalling centres produce growth factors, acting on nearby neural tissue in a concentration dependent manner
Chondrocytes and osteocytes from the maternal perspective
Pelvic area helps protect structures Within pelvic area have ovaries
Where are osteoprogenitor cells found?
Periosteum and endosteum
What surrounds seminiferous tubules (cord in embryos)
Peritubular myoid cells
What does UCP1 do?
Permits the backflow of protons without passing through ATP-synthase during oxidative phosphorylation Consequently, energy is not used to synthesize ATP and is dissipated as heat
What happens to the notochord in lower types of chordates and primitive fish?
Persists into adulthood
Gastrulation
Phase in the embryonic development of most animals, consisting of a complex and coordinated series of cellular movements
Recessive trait
Phenotype is only observable in the homozygote, when the gene function is completely lost
Forward genetics
Phenotype to Gene Used to identify gene by using phenotype
Swyer syndrome
Phenotypically and physiological female, but XY Streak ovaries - like an ovary but not really functional No post-pubertal development of secondary sex characteristics due to lack of hormone production They have no germ cells, but can become pregnant with donated egg
Placenta acreta
Placenta is abnormally deeply attached
Describe Chemically induced pluripotent cells
Pluripotent cells can now be generated from fibroblasts by addition of chemicals
ENU mutagenesis most commonly produces
Point mutations This is what most commonly happens, which makes it good for working out developmental mutations.
'Receptive' endometrial epithelium
Pre-receptive luminal epithelium is nonadhesive To be come receptive, the glandular epithelium becomes highly secretory, the luminal epithelium undergoes considerable changes
Myotome
Precursor cells for muscle The striated musculature of the neck, trunk and extremeties
Ectopic pregnancy What is it? Why does it occur?
Premature implantation outside the uterus factors affect the lining of fallpian cilia, which cant mobilise the zygote thru fall tube to proper cavity
Ectopic pregnancy
Premature implantation outside the uterus - most commonly in the Fallopian tube Results in a non-viable pregnancy and can be lethal for the mother.
What did Down attribute the cause of the syndrome?
Prenatal exposure to tuberculosis
Maternal age effect and Down syndrome
Prevalence occurs with increasing maternal age, as trisomy occurs due to increases in meiotic disjunction that often correlates with increasing maternal age.
Function of tight junctions
Prevent the passage of molecules and ions through the space between cells They block the movement of integral membrane proteins between the apical and basolateral surfaces of the cell
What does capacitation do?
Primes the sperm for penetrating the egg
Two stages of haemopoiesis
Primitive (embryonic) Definitive (adult)
Describe the molecular basis for L-R asymmetry
Primitive node secretes growth hormones: FGF-8 and SHH(Sonic Hedge Hog), cilia directs flow leftwards. Asymmetrical looping of these factors initiates a molecular network controlling: Asymmetrical Looping of the Heart, Gut, Liver, Spleen and lobation of Liver
What happens to the primitive streak?
Primitive streak regresses and extends towards the caudal region by budding off somitomeres (groups of paraxial mesoderm that then compact into discrete bodies called somites)
What cells are not taking part in gastrulation?
Primordial germ cells They are protected from somatic cell differentiation during migration by a complex process of supression
IL-6
Pro-inflammatory factor Important in body regulation, lipid and glucose metabolise
Endochondrocal ossification process
Process by which bone tissue (long bones) is created from cartilage template - occurs during later foetal development 1. Formation of bone collar around hyaline cartilage model 2. Cavitation of hyaline cartilage within the cartilage model 3. Invasion of internal cavities by the periosteal bud and spongy bone formation 4. Formation of the medullary cavity as ossification continues' appearance of secondary ossification centres in the epiphyses in preparation for final stage 5. Ossification of the epiphyses; when completed, hyaline cartilage remains only in the epiphyseal plates and articular cartilages
Situs inversus in humans
Process gone wrong, where the monocilia in the node don't work. They will randomly diffuse to the left or the right, and whichever slide has more (even if this is very slight) they will form on the right It adapts, so everything still joins up But can have problems in fertility - issues in the movement of sperm or eggs
Ossification
Process of bone formation - replacing pre-existing connective tissue with bone Begins during Week 6 of gestation
Goal of the cell cycle
Produce two genetically identical cells from one precursor cell
Progenitor cells (aka transit-amplifying cells)
Progeny of stem cells, but they are not capable of unlimited self renewal They only divide a few times before differentiating
Microvili
Projections that increase the cell's surface area Very important for the small intestine and the kidney, as it helps with re-absorption Made up of acttin
How are neurons generated?
Proliferation in the neuroepithelium of the progenitor cells It is done by symmetrical division to produce more progenitor cells Cells divide with nucleus next to the lumen
UCP1
Promotes production of heat rather then energy in cellular respiration Brown fat is UCP1 positive (white is negative)
When does crossing over occur?
Prophase I
Describe how iPS cell are derived and the pros and cons concerning their use therapeutically.
Pros : avoid the ethical concerns regarding the use of human embryos Cons: huge costs
Role of amnion
Protective buffer against mechanical injury Baby is floating around, so any mechanical stress is buffered out It is fluid filled (water break)
Transcription regulator
Protein that binds specifically to a regulatory DNA sequence and is involved in controlling whether a gene is switched on or off.
Signaling molecules include...
Proteins Small peptides Amino acids Nucleotides Steroids Retinoids etc. They typically act in very low concentrations
Transcription factors
Proteins that directly regulate and drive gene expression by interacting with the promoter of a gene
Signalling molecules include:
Proteins, Small Peptides, Amino Acids, Nucleotides, Steroids, Retinoid, Fatty Acid Derivatives, Dissolved Gases
Cilia
Protrusions from the cell surface
Cillia
Protrusions from the cell surface Can be motile - which helps respiratory surfaces, fallopian tubes Can be immotile - cell signalling
Function of adherens junctions
Provide STRONG mechanical attachments between adjacent cells (e.g. cardiac muscles, epithelial)
Hemidesmosomes
Provide adhesion from cell to extracellular matrix, connect intracellularly to intermediate filaments
Gap junctions
Provide direct cytoplasmic connection between cells They provide ion flow between cells, allowing membrane potential to pass from cell to cell Connexins form channels Most cells use this to communicate Important for heart rate
Role of intermediate filaments
Provide mechanical stability to the cell Takes part in the assembly of the nuclear envelope Supports the plasma membrane when it comes into contact with other cells of the ECM
Actin cortex
Provides framework for the membrane to resist tension Determines cell shape Spans through the cytoplasm
Zonula adherens
Provides some adhesion, ACTIN bundles form belt
Definitive haematopoiesis
Provides the foetus and adult with various cell types that make up the blood It generates haemopoietic stem cells that last the lifetime of the individual
Yolk sac in bird and reptiles
Provides yolk for nutrition
Identify proteins that regulate of cell cycle (checkpoints) and what type of regulators are they?
RB and P53 --> negative regulators
Stem cell concept
RBC are constantly replaced, only 120 days Each day we produce 100 billion They are replenished from a stem cell source
What controls the first cleavage division?
RNA and things from the oocyte, before the zygote has control over things
Cremaster muscle
Raises testes This occurs during sex or under fear stimulus It is skeletal muscle
Two important proteins for cycle checkpoints
Rb and p53
Polyspermy block - 'the fast block'
Reaction that occurs immediately after the acrosome reaction Membrane's electrical potential of the egg undergoes a massive depolarisation through a sodium influx - stopping any more sperm from binding to the egg
Reception of signals usually requires _______ at the cell surface, which bind the signal molecule
Receptor proteins
T lymphocytes
Recognise antigens attached to surfaces of other cells
Achondroplasia
Reduced proliferation of chondrocytes in te epiphyseal plate of long bones Results in dwarfism
2) Achondroplasia
Reduced proliferation of chondrocytes in the epiphyseal plate of long bones, resulting in dwarfism
AGM region
Region where RBCs begin to build up Derived from splanchinic mesoderm, surrounding the dorsal aorta
Placental anchorage
Regulated by the cytotrophoblast When the placenta anchors itself to the uterine wall
Stem cells relationship to the testis
Regulated by the stem cell niche The spermatogonial stem cells sit outside the blood testis- barrier. This is because they don't need to be protected from the immune system - yet.
Basophils
Release histamine in certain immune reactions
Polyspermy block - 'the slow block'
Release of calcium in egg, stimulates cortical granule response. Cortical granules fuse, release their contents into the space between the cell membrane and envelope. Vitelline envelope hardens and permanently blocks further sperm from binding, sperm usually fall off
Stem cells of the gut
Renewal occurs continuously in the lining of the intestine. Stem cells are located at the base of the crypt under the vili. Continually active, they are produced then migrate up to the top of the vili.
BMP4
Required for development of primordial germ cells
Zebrafish research advances
Research focuses on neuronal development, body patterning (the role of specific genes during embryogenesis), cardiac development, muscle development, sleep, regeneration and cancer
How do we know so much about NCCs?
Researcher on chick quail chimeras Graft cells from a quail, add them to a chick and see where the cells end up (through staining) or what they form into
Slow twitch fibres - Type I
Resistant to fatigue, but generate less tension than other muscle types Small fibres Many mitochondria, large amounts of myoglonin
Hyaline cartilage
Resists compression, is flexible Found in the trachea and bronchi, end of bones and inside synovial joints Keeps airways open, creates frictionless movement
Signalling centres
Responsible for patterning embryos can be identified by transplantation experiments
If there is more osteoclast activity then osteoblast activity..
Result in bone mass loss Happens in osteoporosis Bones become more weak and fragile as we age
What causes cellular differentiations?
Result of differences in gene expression Some genes are expressed in all cells, some genes are active only in select specialised cells
Type of transport up the axon
Retrograde
Describe Step 1. Calculation of risk
Risk is calculated by combining the risk due to the woman's age with the risk estimated from serum levels of various biochemical markers.
Somites contain precursor cells for
Sclerotome Myotome Dermatome
Somites contain the precursors for:
Sclerotome - Axial Skeleton Myotome - The striated musculature of the neck, the trunk and extremities Dermatome - Subcutaneous tissue and skin
What are model organisms for gastrulation and why? (2)
Sea Urchins - Easy to see Chicken: - Human and chicken gastrula have very similar morphology - Can be visualised and manipulated - Gastrulation occurs within 5 hours of laying - Anatomical, experimental studies are possible
How do you know a stem cell is a stem cell?
See if you can isolate the cell and make it turn into all of the cells of that tissue Stem cells are also capable of re-populating an organ
How do we produce so many cell types from one precursor stem cell in the blood system?
See the diagram with origin for blood and lymphoid cells - NEED TO KNOW (EXAM?) Shows that the path is very complicated, with many different kinds of precursor cells
Ordered arrangements of somites give way to...?
Segmental partitioning of the spine, neural tube and trunk wall - ribs also
Cells that NCCs can become (and what makes it become that)
Sensory neuron Autonomic neurons Schwann cells ***
Germ cells in the testis
Separated from somatic lineages during early development. Primordial germ cells are protected from somatic cell differentiation
Identify one of the first decisions made by the embryo
Separating the germline from somatic lineages, as they stay protected from signals of other cell types (dont differentiate), and therefore stay pluripotent for a while
What is a gene regulatory region (or sequence)?
Sequence of DNA that a transcription factor can bind to and affect expression of a specific gene
Testis cord formation
Sertoli and germ cells localise to the inside of the cords. Cords are separated from the interstitium (where immune cells are) by basement membrane and peritubular myoid cells. Creates the niche that maintains ste cells and will later direct the progression of spermatogenesis.
Why must vasculature and seminiferous tubules be kept separate?
Sertoli cell blood-testis barrier important bc if germ cells (post meiotic) interact with vasculature, immune cells will recognise
Sertoli cell only syndrome
Sertoli cells are present, but no germ cells in the epithelium This could be due to germ cell migration failure or failure of Sertoli-germ cell communication
How was Dolly cloned?
She was created using the technique of somatic cell nuclear transfer, where the cell nucleus from an adult cell is transferred into an unfertilized oocyte (developing egg cell) that has had its cell nucleus removed. The blastocyst forms and is then transferred into a surrogate mother.
Paracrine signaling
Signal released from a cell has an effect on neighboring cells. VERY common in development, important in organ induction It is secreted into the extracellular fluid For local activity Usually signalling and target cells are of different cell types
Describe neural patterning in the brain
Signalling centres produce growth factors that act on nearby neural tissues in the concentration-dependent manner BMPs, Fgfs, Wnts, Shh
Contact-dependent signalling
Signalling molecule remains bound to surface of signalling cell, it influences only cells that contact it It is very important in development, so communicating cells may send long cytoplasmic processes to contact each other
How does neural tissue develop?
Signals converge on the middle region of the ectoderm and induce it to become neural tissue
Environmental asymmetry
Signals from the direct cell fate Relies on stem cell niche concept, where the niche regulates balance of self renewal and differentiation
Simple cuboidal epithelium
Single layer of cube shaped cells Found in some ducts or glands
Disorder that looks like a mermaid
Sirenomelia Due to issues in BMP, WNT
Mitochondria-rich cell types
Skeletal and cardiac muscle Sperm tail Renal tubular cells
Muscle plasticity
Skeletal muscle can respond to exercise by undergoing hypertrophy Changes are also accompined by changes in gene expression
What tissues are continually renewing in adult life?
Skin Lining of the gut Blood Sperm
Ectoderm epithelial cells
Skin (epidermis)
SKin and nerves in the testis
Skin and nerves are integrated There are lots of innervation of the testis cells This is because they are outside of the body, and are very fragile. It is very sensitive, so your fertility is protected
Why are C. elegans a good model?
Small and transparent Easy to cultivate, grow on agar plates with bacteria for food Have a short life cycle (egg to adult is 3 days) 40% of genes implicated in human disease have orthologues in worms, very similar
Myocyte relationship with the testis
Smooth and skeletal muscles help keep the temperature of the testis at 34 degrees, not the body temperature of 37 degrees. Cardiac muscle are involved in driving blood flow to the testes
What is lissencephaly?
Smooth brain caused by absence of sulci and gyri (folds and bumps in normal human brain)
What muscle type has the highest proliferative ability in adults?
Smooth muscle
Multiunit smooth muscle
Smooth muscle cells are functionally independent, often innervated by single nerve terminal They NEVER contract simultaneously Derived from local mesenchyme They form walls of blood vessels
Key cell autonomous (intrinsic) signals that regulate ISCs?
Snai1 - required to maintain ISCs
Patterning of the spinal cord
Soluble morphogens pattern the DV axis Shh (ventral), BMP (dorsal) play critical role Expression of particular transcription factors controls the type of neuron produced in different parts of the spinal cord Sensitive to the concentration of the signalling molecules
Lateral plate mesoderm fate
Somatic Splanchnic Extra-embryonic
Describe lateral plate mesoderm fate in terms of: - Somatic mesoderm - Splanchnic mesoderm
Somatic Mesoderm (lying closest to ectoderm) causes the formation of the lateral and ventral walls of the embryo Splanchnic Mesoderm (lying closest to endoderm) causes the formation of the wall of the digestive tract e.g. smooth muscle of gut wall
Induction of brown/beige adiposcytes in adipose depots
Some of the things that can induce brown fat are not good long term. So brown fat could be an anti-obesity to target, but need to find the right way
How can organisms have blue blood?
Some organisms use hemocyanin instead of haemoglobin It contains copper, so it is blue
Paraxial mesoderm gives rise to?
Somite and Head
Regulation of somitogenesis
Somites are specified along AP axis by Hox gene patterning
Golgi
Sorts, modified and packages the cellular products that have passed through RER and SER
Tangenital migration
Source of how neurons get to the cortex Migrate on a a tangent (wiggly pattern) They develop into interneurons, in specific layers of the cortex
Primordial germ cell journey
Specification Commitment Migrations Colonisation See lecture about this for more details
Describe primordial germ cell journey in humans: - Specification and commitment
Specification and commitment - Little is known of the earliest stages of human germ cell development, but embryonic stem cell approaches are now allowing this period to be investigated
Master genes
Specify cell lineages e.g. determine if a cell becomes a limb muscle. If this is gene is expressed somewhere else, it will be able to determine that whole program.
Sperm and oocytes have what chromosomes?
Sperm X or Y Oocyte only X
What is unification?
Sperm and egg pronuclei unify after fertilisation
Specialised features of spermatozoon
Sperm cells have three regions, - the head (acrosome and nucleus) - the mid-piece (mitochondria) - tail (flagellum)
Point of the blood-testis barrier
Sperm produced in testis are a different cell, so immune system would try to kill it So basically blood-testis barrier keeps the immune system from getting to it - do't want to pierce this barrier
Oogensis and spermatogenesis - DIFFERENCES
Spermatogenesis has equivalent meoitic divisions, resulting in four equivalent spermatids While oogenic meiosis is asymmetrical = only one egg is formed together with three polar bodies. They also have different timing of maturation
Journey of sperm
Spermatogenesis occurs in the seminiflerous tubules of the testis to produce sperm. They leave the testis through the epididymis.
Developmental order of sperm
Spermatogonia Primary spermatocyte Secondary spermatocytes Spermatids Spermatozoa
Caudal neural tube defect
Spina bifida
Astrocytes
Star like in shape Basically just clean up neurons Invovled in nutrient supply, structure, clean up synapses and phagocytse debris
Explain the concept of a stem cell niche and some examples
Stem cell niche is the environment surrounding a SC e.g. surrounding cells, ECM, secreted growth factors, signals from basement membrane
Umbilical cord blood transplant.
Stem cells are taken from an umbilical cord are less prone to rejection.
Divisional assymetry
Stem cells have an internal assymetry, and when it divides the daughters receive different determinants This will effect which will become a progenitor cell and which will be a stem cell
Totipotent
Stem cells with the potential to differentiate into any type of cell.
Urogenital crest
Structure that is the origin of the kidneys and gonads --> urogenital system
Anatomical distribution of adipose tissue
Subcutaneous adipose tissue: Abdominal and Femoral Intraabdominal adipose tissue: Visceral and retroperitoneal Other Depots: Intra and intermuscular, perivascular and epicardiac
How can epidermal stem cells be used for tissue repair?
Take an epidermal stem cell, and put in ex vivo conditions that maintain the population. Use genetic engineering to induce skin cells.
Describe an experiment that will test if a tissue is determined
Take region from chick embryo that normally forms ribs and transplant into cervical region. If ribs grow in the cervical area then this experiment proves that the donor tissue is determined as the fate of the tissue is not reversed even when placed in a different region of the embryo
Ex vivo experiments
Take tissue developing in an emrbyo, take it out and put it into culture in the lab
Sperm motility
Testicular sperm can't swim Once they leave through the epididymis, they acquire motility. They get FULL motility when they reach the female reproductive tract
What is not correct regarding transcription factors (e.g. SRY)?
That it can be expressed anywhere in the cell, it is only expressed in the nucleus
Example of a defect experiment
The Apical Ectodermal Ridge (AER) experiment - the AER is a structure present in developing limb buds If they removed it in an early stage, you get a truncated limb. The later you remove it, the less you lose (e.g. you just lose the digits)
From G1 to S, what happens?
The Cyclin D-CDK4 complex determines whether cell cycle continues This starts a pathway which prepares the cell for S phase
How do we find out which of the many genes on Cr21 are actually affecting development?
The abnormal expression of the 310 genes (mostly increased protein levels) is expected to generate the multiple abnormalities observed in development BUT a lot of them are dosage-sensitive, as the cell tightly regulates expression.
Example of a defect experiment
The apical Ectodermal Ridge (AER) is a structure present in developing limb buds. Therefore, removal of the AER results in truncation (premature termination of protein elongation of developing limbs
Development of bone
The axial skeleton is initially deposition as cartilage, then acts as a template for later bone formation
What if bone was just composed of inorganic ECM?
The bone would be very brittle. If it was exposed to a strong force, it would shatter.
What is brain-testis moleculer link
The brain influences the ability of the testis to fulfill its function! e.g. Mating behaviours (eg seductory or dominance behaviors) enable a male to mate with a female!
1) Osteoarthritis
The cartilage covering bones (hyaline cartilage), particularly at high stress joints, thins over time, resulting in a "bone against bone" joint. This leads to reduced motion, and pain.
Active movement of PGCs
The cells themselves move to the gonads are being formed
Where is there no connective tissue?
The central nervous system
Chick quail chimeras result
The chick that formed with some quail cells went on to form part of the wing. It formed the pigment cells of the wing (not the structure itself)
Day 19-21 of human embryonic development
The chordal process Primitive streak is lengthening out as the embryo also lengthens
Describe notochord development at day 22-25 of human embryonic development
The chordal tissue breaks away from the endoderm (endoderm fuses again) and the ectoderm, in order to form a complete cord: notochord
Describe notochord development at day 20
The chordal tissue forms the chordal plate by bonding with the endoderm and subsequently separates
Therapeutic cloning
The cloning of human cells by nuclear transplantation for therapeutic purposes, such as the generation of embryonic stem cells to treat disease.
Knockout
The complete inactivation of a particular gene in an organism. = Null mutation Eg Gene targeting in mice
Blood islands - primitive haematopoiesis
The consist of haemangioblasts Appear in week 3 Central cells form blood cells, peripheral cells become endothelial cells of blood vessels
Slow block
The cortical reaction, in which cortical granules modify the zona pellucida
What is the source of all germ layers (and therefore all tissues and organs in the embryo)?
The epiblast, through gastrulation
Where does the sperm leave through?
The epididymis
Ventricles
The fluid filled space in the brain Contains cerebrospinal fluid
Neurulation
The folding up of the neural plate to form the neural tube The brain and spinal cord maintain a tube like structure with a fluid filled space in the centre Epidermis forms as a seal over the top - becomes the skin
Colony Forming Units (CFUs)
The growth and differentiation of progenitor cells into colonies, controlled by CSFs
Human embryo at 8 weeks (sex systems)
The indeterminate genital ridge has Mullerian ducts (female) AND Wolffian ducts (male).
What is the matrix of blood?
The liquid, plasma Plasma is dissolved proteins in water
What does it mean if the proper Mendelian ratios are not obtained?
The loss of the gene results in embryonic lethality
Identify difference between blastocyst vs Embyro
The main difference between blastocyst and embryo is that blastocyst is a thin-walled hollow structure from which the embryo arises whereas embryo is the early stages of the placental development from which the fetus arises
Inner cell mass
The mass of cells in the blastocyst that ultimately give rise to the embryo and other embryonic structues (the amion, the umbilical vessels, etc.)
In some patients with a condition called Hirschsprung's disease, there is a nonsense mutation in the first exon of a gene called Sox10. What is the effect of this kind of mutation?
The nonsense mutation means there is a stop codon, therefore causing premature termination of the translated protein.
Interkinetic nuclear migration
The nucleus of the dividing cell moves basally in S phase and to the lumen in mitosis The progenitor cell undergoes symmetrical division to produce two more progenitor cells
What is key for the cell-cell communication?
The plasma membrane, through having receptors on the cell This allows it to receive messages such as differentiate, grow and divide, survive or die
Indirect immunofluorescence
The primary antibody is unlabelled Antibody will bind to the antigen, unbound will wash away. Secondary antibody with fluoro staining will then bind to the primary a
Thermodynamic model of cell interactions
The quantity and the strength of the binding mediates the formation of embryonic structures Cells trade weaker bonds for stronger bonds, so find cells with the same type of adhesion molecules This results in a the cells being sorted
What triggers the process of cell death in the nervous system?
The target tissue regulates the number of axons innervating it
Testosterone production
The testes is communication with the brain Leydig cells produce testosterone
Why is the ductus deferens so long?
The tests was once up in the abdomen, and then moved down. So now it seems very long but was necessary
In the process of implantation of the blastocyst, what cells need to interact and how?
The trophoectoderm and the blastocyst They have to appose and adhere to the endometrial luminal epithelium
What drives the budding off in somitogenesis?
The waves of signalling
What is different between compact and trabecular bone?
Their composition is the same Only the 3D arrangement of the components is different
Define therapeutic cloning
Therapeutic cloning or somatic nuclear transplantation could be used to produce *patient specific ES cells*
Methods to obtain pluripotent, patient specific cells?
Therapeutic cloning to generate ES cells Induced pluripotential Stem (iPS) cells
How are epithelial cells orientated?
There are always a lumen (except for skin, where lumen is the outside) Base Apex
How are stem cells involved in spermatogenesis
There are spermatogonial stem cells sit OUTSIDE the blood-testis barrier! - Continuously replenish the spermatogenic process
Why might we not see a phenotype in a knockout mouse even though that signalling molecule is in the area?
There can be redundancy between signalling molecules, particularly between those in the same family. To test this, can do a double or triple knock-out.
Transcription/translation is very tightly controlled - what does this mean in terms of expression of abnormal chromosomes?
There is multiple layers of feedback regulating expression. So, even with an extra copy of a gene, a normal balance would be achieved.
Why is the fetus not rejected by the maternal immune system?
There is reprogramming of the maternal immune system. Uterus contains unique immune cells that don't circulate anywhere else in the body e.g. uterine NK cells which play a role in spiral artery remodelling
Role of immune system in testicular development
There were many immune cell types are present in the interstitial spaces of the testis. Think that macrophages play an essential role in setting up testicular structures If they are knocked out, then development is seriously limited
Major functions of brown adipocyte
Thermogenesis and can secrete hormones It is UCP1 positive
Ethical issues of therapeutic cloining
These cells are still produced using a human embryo. Nucleus of an adult's somatic cell is transferred into an oocyte. It develops, cell from the blastocyst is taken and cultured.
Histological features of cardiac muscle
They are attached end to end - no fusion of cells It is striated, but you can see that the cells are branched Points where cells are attached are called intercalated discs Have a central nucleus, that is oval and pale
Formation of lymphatic vessels
They are initiated from a subset of endothelial cells, sprouting from the cardinal vein. Prox-1 and VEGF-C are critical for their formation
Embryonic erythrocytes
They are large and nucleated, expressing embryonic globin genes For the first six weeks, almost all circulating RBCs are derived from the yolk sac
Mouse research advantages
They are mammals Very similar to physiological systems of humans They develop a range of similar diseases that affect these systems, and certain diseases not normally experimented by mice can be experimentally induced
Organisation of brown adipocytes
They are organised into discrete lobules, surrounded by connective tissue Extensive blood vessels and numerous sympathetic nerves are terminating on the adipocytes and blood vessels
Why are iPS considered to have strong therapeutic potential?
They are patient specific Have potential to form any clel type
Lymphatic vessels
They are separate from the blood circulatory system, draining fluid and transporting lymphocytes
Osteocytes in compact bone
They are trapped in lacunae (small spaces) They receive nutrients and remove waste products via cytoplasmic processes, that connect to neighbouring osteocytes and the central canal This is because nutrients are unable to diffuse across calcified bone matrix This allows an osteocyte that is embedded deeply to still be connected
What do skeletal muscle look like?
They are very long, with fused cytoplasms and multiple nuclei Nuclei are placed towards the peripherary Have a lot of blood vessels
Monocytes
They are vigorous phagocytes that destroy bacteria and active other immune cells They present antigen to T lymphocytes When in connective tissue, become macrophages
What do neurons do once they are born?
They can't stay in a single layer - they migrate away from the ventircal surface (closer to the outside of the brain) Can use the process of the apical progenitor cell to the outer part of the complex
Spermatogonial stem cells
They continuously replenish the spermatogenic process Spermatids have cytoplasmic joining so they can share some of its material (for its sex chromosomes, so all the spermatids are equal). Only when they are released will they break this joining.
After oogonia arrive to gonads..
They enter meiosis, but arrest at prophase I of meiosis I until puberty
Why are germ cells considered to be immortal?
They form the link between generations, as only a germ cell will be passed on (rest of the ells will die with the person) A germ cell is define
When do sperm acquire motility
They gain motility through the epididymis but don't acquire full motility until they reach the female reproductive tract "capacitation"
Do blood vessels grow from the heart?
They grow independently and everything ultimately joins up.
Arrangement of microtubules in cilia and flagella
They have a 9 + 2 arrangement 9 fused pairs on the outside of a cylinder, 2 unfused pairs in the centre Dynein arms attached to the microtubules and serve as molecular motors
Why are there epithelial cells avascular?
They have underlying connective tissue which have blood vessels But it does have nerve endings
Histology of fat cells
They look empty, as fats are extracted during histological processing of tissue
Dense regular connective tissue
Thickly packed parallel fibre bundles Relatively few fibroblasts Resists force in one direction Eg. Tendons, ligaments, bone, some organs
Dense regular connective tissue
Thickly packed parallele fibre bundles, few fibroblasts They resist force in one direction e.g. tendons, ligaments, bone, some organs
How can we change the expression of a Developmental gene ?
This can be achieved by making transgenic animals.
Transgenic approaches can be used to alter the expression of genes in many different model organisms.
This method allows hypotheses about gene function to be tested functionally within animals
Carniofacial anormalities in DS
This phenotype is observed in Ts65Dn mice. May be related to specific changes in bone development. Thought to be caused by migration and proliferation defects in neural crest cells in the developing embryo, due to an altered response to sonic hedgehog.
How does Notch work?
Through lateral inhibition An active Notch pathway makes an absorptive cell, inactive Notch pathway makes secretory
How are blood cells formed?
Through repeated cell divisions Cell specialisation generates the many cell types, but many will die
How does sperm leave the testis?
Through the epididymis
Zonula occludens
Tight junctions Tight seal, no flow of material
Types of junctions
Tight junctions Adherens junctions Desomeres Gap junctions Hemidesomosomes Focal adhesions
Changes to the receptive phase of the epithelium
Tight junctions refrain a blastocyst from implanting - they move out of the way so blastocyst can implant.
Passive movement of PGCs
Tissue moves, so the cells are taken along too
Issue with areas wth high self-renewal
Tissues that contain stem cells that can rapidly repair damage are prone to cancer (e.g. bowel cancer, skin cancer)
What causes lineage specification and restriction of developmental potential?
Totipotent cells of the epiblast differentiate More restricted in their developmental potential as gastrulation and embryogenesis proceeds
Gene regulatory networks
Transcription circuits, where there are different effects of activation and repression
How can positive feedback loops create cell memory?
Transcription regulator A is required for the transcription of its own gene. It starts being produced due to a transient signal turning on expression. Gene A continues to be transcribed because regulatory A is continually activating it (the gene a protein acts as its TF) So even though the transient signal is now gone - gene A continues to be transcribed
How can we test whether a cell at a specific stage of development is determined?
Transplantation experiment (put it into a different embryo)
Signalling centres responsible for patterning embryos can be identified by?
Transplantation experiments.
Therapeutic cloning
Transplantation of a somatic cell nucleus into an enucleated oocyte, which then goes on to produce a blastocyst
Lipid stored in adipose tissue as mainly?
Triglycerides i.e. esters and glycerol
Explain maternal artery remodelling
Trophoblast invade into maternal spiral artery to widen diameter, make them non-contractive, so no contraction but rather pooling of blood
Trophoblast is derived from what?
Trophoectoderm
Where is the trophoblast derived from?
Trophoectoderm
Why do we have so many eggs before birth and they are lost?
Try to weed out the 'bad' eggs, so during puberty best ones are left
Name of mouse model that has provided a lot of data on genes involved in Down syndrome, and been used for therapy
Ts65Dn
What is the most 'faithful' model of DS?
Ts65Dn mouse - it carries 132 genes that are syntenic with human Chromosome 21
Intestinal cancer
Tumours may be seeded and maintained by a small population of 'cancer stem cells' Intestinal tumours progress from a benign polyp, to an invasive carcinoma
Cyclins and cyclin-dependent kinases
Two key classes of regulatory molecules They determine a cell's progress through the cell cycle
Are NCC progenitors really multi-potent? Limitation of grafting experiments
Two possible options They are different cells that were grouped together so couldn't tell them apart, but could only form one fate. Or have a stem cell that can form all of the cell types. Grafting cells cannot tell this apart, need another test
Organic bone extracellular matrix
Type I colagen fibers Various non-collagen proteins that are uniqu to bone and assist mineralisation Tough and flexible
Reticular fibres
Type of collagen (3D scaffold) Delicate, fine networks that give support to individual cells
Characteristics of white adipocytes
UCP1 Negative Low Mitochondria density One large lipid droplet Major Functions - Energy Storage - Endocrine (leptin, adiponectin)
Characteristics of brown adipocyte
UCP1 Positive High Mitochondrial density Numerous small lipid droplets Major Functions - Thermogenesis - Endocrine (e.g. FGF21)
Characteristics of beige adipocytes
UCP1 Positive Medium mitochondrial density Few to many lipid droplets
How were flaws in human developmental biology originally detected?
Ultrasound It has enhanced a lot to give a 3D image.
Coordination of the regulation of fat deposition and fat mobilization
Under fed states, energy that comes into the gut. The triglycerides are made into fatty acids. During fasting, fat is mobilised and burnt to provide energy.
Describe the non-receptive early secretory phase
Under normal circumstances, endometrium is 'non-receptive' to blastocyst i.e. it is refractory - wont adhere, is deterred from adhering
Myoblasts
Undergo frequent divisions They undergo normal mitotic cell division, but then undergo coalesce to form multinucleated synctial muscle fibre The nuclei are located centrally in the fibre at the start, then move gradually displaced to the peripherary
After gonocytes arrive to gonads..
Undergo mitosis-arrest-mitosis At birth will keep developing Don't enter meiosis until puberty
Functionalis layer of endometrium
Undergoes changes during each menstrual cycle, but is shed if implantation does not occur
Lack of space between epithelial cells
Unlike other cells, they are very close together Helps lumen form nice tubes
Metabilosation of BAT fatty acids
Unlike white fat, the liberated fatty acids are metabolised quickly Heat production is increased in these cells because the mitochondria have in their inner membrane protein UCP1
How many follicles mature each month?
Up to 50, but only one will continue to become te egg Probably a way to ensure strongest survives Dominant follicle enlarges, becomes FSH-independent but the rest of the follicles still need it - so they will die.
Gene activity during development of skeletal muscle fibres
Upstream activators are on mygoenic progenitor cells to start the driving of the muscle cells Sequence of genes that will be switched on that drive muscle cells through their different fate stages
Frog early research
Urine of pregnant women were injected into female frogs, and frogs laid eggs due to presence of hormones It was the fastest and most reliable pregnancy test in the 1960s.
How can we detect a specific cell type in a tissue section?
Using an antibody against a protein that is only in that cell type Can be tagged using an enzyme or a fluorescent marker
Reverse genetics
Using the gene to find the phenotype. Identify developmentally important gene and introduce specific mutations. Analyse the developmental consequences.
Forward genetics
Using the phenotype to find the gene Spontaneous mutations or deliberate mutagenesis results in developmental abnormalities. This can be used to identify the mutated gene.
Mitochondrial defects
Usually if something is wrong, if is not compatible with life Sometimes defects can be minor, causing 'exercise intolerance'. Can also result in disorders with vision is lost
Where are smooth muscles located?
Usually lining hollow tubes or hollow organs
Function of the vasculature
Vasculature is all outside the codes, Sertoli cells provide all the nutrients. We need the Sertoli cell blood-testis barrier once spermatogenesis commences
Two processes that develop blood vessels
Vasculogenesis and angiogenesis
Order of blood vessel processes
Vasculognesis occurs first, as it is the creation of blood vessels Then angiogenesis occurs, were the existing vessels are extended and remodelled
What is the function of the umbilical vein and artery?
Vein carries oxygenated blood to the placenta Artery carries deoxygenated blood away from the placenta
Sclerotome forms..
Vertebrae and rib cartilage
Cardiac muscle regeneration
Very bad regeneration - muscle dies
Human studies for DS
Very difficult to go from mice to human Some studies have happened in human adults, as they can give consent But no studies have yet been performed on infants Evidence that permanent brain alterations originate during fetal life.
Stem cell research into cartilage
Very important, as it doesn't regenerate very well It also isn't vascularised, so it won't have the rejection of tissue
How do axon guidance work intracelluarly?
Very localised affect on the microfilaments in the growth cones It can have positive (polymerisation of actin filaments) or negative (dissassembly of actin filaments)
Immunohistochemistry v immunocluorescence
Very similar, both detect the location of proteins and other cellular molecules They just do it in different ways IHIC uses enzymatic reation to label molecules Immunofluorescence uses fluoresecent tags
Haemopoietic stem cells (HSC)
Very well characterised It is pluripotent It can self-renew, and produce commited progenitors
Apoptopic bodies
Vesicle structures which are broken down into contained vesicle structures
Haemochorial
Vili are bathed in maternal blood, to facilitate increase in transport of gases
Placental villi
Villi floating in the intervillous space, bathed in maternal blood
Intraabdonimal adipose tissue
Visceral (mesentric and omental) Retroperitoneal (prerienal and perigonadic)
What triggers apoptosis?
When an essential factor is removed from the extracellular environment or an internal signal is activated
G0
When cells (e.g. nerves) never leave G1 stage, it is called G0
Eyeless (ey) transcription factor in drosophila
When ey is switched on, it then switches on a cascade of genes that drive eye development...even when switched on in the wrong place...
FGF receptor
When normal, effects chondrocytes When mutated, growth plate becomes disorganised so no region of proliferating chondrocytes
Homeotic transformation
When one body segment is transformed into another with different positional identitiy
Dominant trait
When the phenotype is observable in the heterozygote mice when gene function is partially lost.
Consequence of excess white adipose tissue
White adipose tissue appears histologically and physioligcally similar, differences are in gene expression. More visceral (abdomenal) have an increased risk of diabetes and cardiovascular disease. Subcutaneous deposits of white fat do not have the same risks
What happens to the hypoblast?
Will spread, and becomes primary yolk sac. As development progresses, primary yolk sac develops further into the secondary yolk sac.
Key niche (extrinsic) signal that regulates ISCs
Wnt and Notch notch works by lateral inhibitiron - when activated, cell is fated to form an absorptive cell cells adjacen to notch, turn off signal and express moelcuel delta, inactive notche pathway and goes down secretory celll lineage if you inactivtate notch, end up of intestinal tract full of secretory cells and lack absorptive cells if u overactivate notch, end up woth the opposite
Niche signals in the intestine that regulate intestinal stem cells
Wnt and Notch When Wnt is active, cells proliferate. It is really important for the maintenance of cell numbers. Notch is important for what cells are made. When Notch is active, it makes absorptive cell. If Notch is inactive, it makes a secretory cell.
In male embryo, reproductive system
Wolffian ducts develop into the vas deferens, prostate and seminal vescles. Mullerian ducts degenerate
What do Wolffian ducts develop into?
Wolffian ducts develop into the vas deferens, prostate, and seminal vesicles, and the Müllerian ducts degenerate (anti-Müllerian hormone - AMH)
Dense irregular connective tissues
Woven patterns of fibres Resists tension/stress from any direction Eg. Dermis of the skin, non-lactating breast
Dense irregular connective tissue
Woven patterns of fibres, that resists tension/stress from any direction E.g. dermis of the skin, non-lactating breast
Turner syndrome
XO female
Go over the overview of making of a testis
XX
Leukaemias
XX
B lymphocytes
XXX
Risk factor of leukaemias
XXX
T lymphocytes
XXX
Kleinfelter
XXY, male
SRY location
Y chromosome
Is brown fat present in adult humans?
Yes
Labelling cartilage in report
You can say what structure it will become (e.g. this is cartilage that will form a vertebrae)
Why do we have different types of asymmetrical cell division?
You don't want to deplete progenitors, once neurons are born they don't divide. Need to maintain enough progenitors to populate the whole NS. Type II results in more neurons then Type I. Increased basal progenitors correlates with giri - bumps on the brain - more neurons.
Why doesn't OPT work with humans?
You have to pass the light through an embryo, can't do that with humans as unethical. So do it with mice
How do we generate a mouse line from a chimaera?
You need to breed the chimaeric mouse to a wild type mouse. Not all chimeras will have the recombined gene in the germ line. So if you breed a chimeric mouse to a WT, and it shows phenotype of chimeric mouse then it shows that the recombined gene will be in that mouse.
What if bone was composed of organic ECM?
You would have something that is really tough, but it would also be really flexible (could tie our bones in a knot). This obviously doesn't give support, so we have inorganic minerals
What events occur once the sperm head enters the egg? Select all answers that apply. a. unification/syngamy b. sperm head undergoes mitosis c. implantation into the uterus d. sperm centriole directs formation of chromosomes along the mitotic spindle e. polar body directs cleavage pole f. female pronucleus completes second meiotic division
a d e f
Positive feedback loop
a feedback loop in which change in a system is amplified Master transcriptor regulators can regulate expression of many other transcription factors
Synaptic signalling
a nerve cell releases nerotransmitter molecules into the synapse, stimulating the target cell
herapeutic cloning describes the process where: a. mature cells are treated with retroviruses to make stem cells. b. patient specific ES cell lines could be generated. c. multipotent stem cells are isolated. d. a complete genetically identical human is born.
b. patient specific ES cell lines could be generated.
Abnormalities in keratin causes what to skin?
blistering
Sinusoids
blood-filled spaces
BAT colour is due to?
both the numerous mitochondria - containing coloured cytochromes - scattered through the adipocytes and the large number of blood capillaries in this tissue
ENU mutagenesis most commonly produces: a) chromosomal rearrangements b) small deletions c) small insertions d) point mutations e) gene deletion
d) point mutations
gastrulation occurs from what days?
d8-15 post fertilisation
Compact bone
dense and solid
What do somites develop into?
dermis, skeletal muscle, cartilage, tendons, endothelial cells
Gene manipulation
developing organisms is used to alter the expression pattern of genes within the embryo, and test hypotheses about the developmental function of these genes.
What happens in cilia doesnt work?
diffusion and different concentrations will cause organs in different places of the body
Sagital plane
divides body into left and right
KO Expression of Fgf8 in an early mouse embryo (E7.5)
embryo dies at E8
2 ways for stem cells to produce daughters of different fates?
environmental and divisional asymmetry
Segment polarity genes
establish anterior-posterior gradient within each segment If mutated, segments are replaced by their mirror images
Not Determined
fate can be reprogrammed by environment
Fate mapping
general territorial diagrams of embryonic development Generated using markers or genetic manipulation.
Sertoli cells
germ cell "nurse" cells
Define Pluripotent and give an example
gives rise to cell derivatives of all three germ layers. e.g. embryonic SCs
Define Multipotent and give an example
gives rise to multiple cell types but does not normally generate cell types from all germ layers e.g. Haematopoetic SCs
What does placenta secrete
hCG progesterone + estrogen
Heterochromatin
highly condensed chromatin Hard to transcribe
Function of placenta
hormone synthesis and secretion and growth factor synthesis and secretion
Describe induced pluripotent SCs (iPSC) and how its derived
iPS cells skin biopsy from patient, 4 key transcription factors can be transfected into cultured skin cells, turn into iPS cells after a few weeks iPS cells can be differentiated in vitro can take cells from patient with degernative disease, culture them, by genetic engineering repair defect in cells, produce healthy cell type, and transplant back into human
Females have more subcutaneous fat where?
in hip and thigh
What happens when there is an extra notochord? (transplant Shh)
induces second set of motor neurons
What hormones control adaptive thermogenesis through regulating SNS?
insulin, leptin, BMP8B, GLP-1 and T3
Functional evidence
loss of function. Remove the process or molecule
Defective dynein arms cause what?
male infertility and also respiratory tract and sinus problems
Cartilage is characterised by?
material associated with collagen - hyaluronic acid
KO Expression of Fgf5 in an early mouse embryo (E5.5)
mice have long hair
What are microtubules regulated by?
microtubule-associated proteins (MAPs) - can stabilize or destabilize microtubules
Give examples of slow responses to extracellular signal
minutes-hours (usually intracellular receptors) - Increased cell growth and division - Involve changes in gene expression
Abnormalities in desmin causes what
muscular dystrophhy
Describe how ICM must be positioned in apposition
must be directly apposing the uterine wall otherwise cannot attach
Describe what a pre-receptive luminal epithelium means
nonadhesive
What are the 6 actin genes humans have and what do they encode?
o 4 encode alpha-actin - muscle cell contraction o 1 beta-actin - front of moving cells o 1 gamma-actin - stress fibres
Describe S phase control
o Active S cyclin-CDK complexes phosphorylate proteins that make up the pre-replication complexes on DNA replication origins o Scattered all over chromosomes and genome o Once bound and replicate DNA, part of the proteins move away from replication site so this ensures that: • Each pre-replication complex is activated to initiate chromosomal replication • New complexes are prevented from forming • The genome is only replicated once
What causes lissencephaly?
o Caused by abnormality in neuronal migration
Describe how intermediate filaments are organised in: - epithelial cells - primary fibroblasts
o Epithelial cells: intermediate filaments are distributed all over the cytoplasm and attach to nucleus o Primary fibroblasts: vimentin is oriented towards the periphery and spans neither the whole cytoplasm nor is it connected to cell-cell-adhesion sites
• Transformation of lean to obese adipose tissue there is increase in deposition of triglycerides which lead to:
o Release of chemokines that induce recruitment of macrophages from the bloodstream increases infiltration and inflammation ↑TNF-α and IL-6. o Leads to ↑ FFA and dysregulated secretion of hormones which all act in a paracrine or autocrine way, o Leads to decreased muscle and liver insulin sensitivity through resulting in increased liver glucose production
Distinguish between the 2 types of asymmetrical division
o Type I - generates another apical progenitor and a neuroblast (neuron) o Type II - produce apical progenitor cell and basal or progenitor, which divides at least once prior to differentiation into neurons
Explain how contact dependent signalling inhibits neural differentiation?
o Vertical division of 2 cells, one cell expresses neuronal gene which produces ligand which binds to Notch receptor and tells cell to stay progenitor, and the other one becomes neuron Binding go the notch receptor results in transfer of part of the receptor to the nucleus - where it blocks expression of neural genes
At way days does Early Implantation occur?
occurs at time of implantation: day 6-8
What is somitogenesis
occurs via a clock-wavefront model, in which waves of developmental signals cause the periodic formation of new somites
Direct immunofluorescence
primary antibody that binds to the antigen has a fluroescent marker that can be detected by a fluoro microscope The unbound antibody has to be washed off
When does estrogen peak?
prior to ovulation AND receptive stage
Endocytosis
process by which a cell takes material into the cell by infolding of the cell membrane
What does it mean to be "immune privileged"? Give examples of tissues
protected by the blood-testis barrier formed by Sertoli cell tight junctions - Central Nervous System - Eye - Uterus - Testis
Trisomy 21 causes what detriments?
reduction in brain volume, with the hippocampus and cerebellum particularly affected. A similar phenotype is observed in the Ts65Dn model
Mature somites are separated into what 3 compartments?
sclerotome myotome dermamyotome
Single squamous epithelium
single layer of flat cells. lines blood vessels, including capillaries, where gas exchange occurs
Glandular epithelium is tortuous - what does this mean?
spiralled and curved, to increase SA for secretions that migrate up to luminal surface
Signals from neighbouring cells
start off with set of cells that express a protein, prot secreted. cells close to set of cells exposed to high conc and cells further away exposed to lower conc. cells closer adopt a new fate (blue)
What happens once ovulation occurs?
surrounding follicle that housed the mature oocyte becomes the corpus luteum. This secretes high conc of prog (seen in purple surge), to support implantation. Correlates with the thickening of endometrial lining.
Morphogenesis
the development of the form of an organism and its structures e.g. gastrulation
Explain what interkinetic nuclear migration in neurogenesis is?
the nucleus of the dividing cell moves basally in S phase, and to the lumen (ventricular surface) in mitosis. The progenitor cell on the right undergoes symmetrical division to produce two more progenitor cells
What happens to adipose tissue post-menopause?
there is redistribution of adipose from sub to visceral region. Hormones like estrogen may cause this redistribution
Progenitor cells or transit-amplifying cells are progeny of stem cells but ?
they are not capable of unlimited self renewal and only divide a few times before differentiating.
How does the functionalis layer prepare for pregnancy?
undergoes changes during each menstrual cycle, but is shed if implantation does not occur
How long can sperm last in the female reproductive tract to fertilise ovum
up to 5 days
Electron microscopy
uses electrons instead of light, the shorter wavelength of electrons gives greater resolution e.g. used for internal mitochondrion viewing
Signalling molecules act at what concentrations?
v low <10^-8
What happens in the secretory phase?
vasculature becomes highly tortuous, long and highly brnaching at secretory phase. vascular is constantly changing as well.
Fibrous cartilage
very tough form of cartilage found in the intervertebral disks of the spine
Synctium
when a single cell membrane surrounds multiple nuclei Male germ cells don't complete cytokinesis during spermatogenesis, so cytoplasmic bridges maintain connections
What is the function of the female reproductive tract?
xx
At how many weeks do the ducts differentiate?
~10 weeks in human embryo
Placenta acreta Define Cause Treatment
• Abnormally deep attachment of the placenta • Cause? Possibly a defect in the decidua • Treatment: Caesarean section and hysterectomy
Growth factors acts on who?
• Act on the placenta/fetus • Act on the mother
What filaments are required in neuronal migration?
• Actin filaments required for migration and cell adhesion
Cell types in WAT
• Adipocytes (lipid-filled cells) 30% • Preadipocytes and fibroblasts • Matrix of collagen fibers • Blood vessels - capillaries/endothelial cells • Immune cells - monocytes/macrophages, lymphocytes
Consequences of excess white adoposity
• Although all white adipose tissue appears histologically and physiologically similar, differences in gene expression have been noted between • Visceral deposits (in the abdomen) • And subcutaneous deposits of white fat. • Such differences may be important in the medical risks of obesity; it is well-established that increased visceral adipose tissue raises the risk of diabetes and cardiovascular disease whereas increased subcutaneous fat does not. • The release of visceral fat products directly to the portal circulation and liver may also influence the medical importance of this form of obesity.
Role of hCG?
• Basis of urinary pregnancy tests • Produced by trophoblast prior to implantation • Maintains corpus luteum production of progesterone & estrogens • Maintenance of pregnancy
Cytoptrophoblast
• Beneath syncytiotrophoblast • Cell column • Proliferative & invasive
Describe blastocyst implantation
• Blastocyst apposes the uterine luminal epithelium (LE) • Trophectoderm (outer layer of blastocyst) - attaches to the uterine luminal epithelium • Trophoblast differentiate from trophectoderm, then invade between epithelial cells to form placenta
Preeclampsia - Characterised by? - Cured by?
• Characterized by: Hypertension, proteinurea after 20 weeks • Cured by delivery of placenta
Treatment of ectopic preg?
• Chemotherapy (methotrexate) - bc trophoblasts are highly proliferative and invasive, so chemo targets these and only works if used v early • Surgical - remove Fallopian tube
Role of chondrocytes
• Chondrocytes make up the cellular matrix of cartilage • Support and repair the cartilage matrix • Facilitate the exchange of materials between cartilage and surrounding • tissues • Not capable of cell division
In what way does the neural tube close? and why is this process important?
• Closes at about the middle first, then zippers up in both directions • It is open on both ends (neuropores) - these need to be closed for normal development of brain and spinal cord
How do you get a layered cortex?
• Combine Cortical and Tangential Migration to get a layered cortex
L8 What does the nervous system develop from? Where does neural plate come from?
• Comes from ectoderm germ layer • Neural plate comes from middle region of ectoderm, induced to form in the middle as signaling molecules are positioned there
Role of microfilaments?
• Cytokinesis during mitosis is dependent on actin filaments/cytoskeleton • Essential for cell migration
What is the actin cortex? where does it sit?
• Dense network called actin cortex is just under plasma membrane • Actin cortex provides framework for membrane to resist tension, and determine shape of cell
Describe spiral artery remodelling
• Endovascularextravillous trophoblast (eEVT) + immune cells destroy endothelial and smooth muscle cells lining uterine spiral arteries • They reline them by producing & embedding themselves in fibrinoid • This reduces artery resistance & increases blood flow
What hormones is the human menstrual cycle regulated by?
• Estrogen • Progesterone
What are extrinsic mechanisms?
• Extrinsic mechanisms would be extracellular signals, between o Daughter cells (1) o A daughter cell and surrounding cells (2), or o The precursor cell and surrounding cells (3)
What subunits form filamentous actin?
• Globular acting (G-actin) are monomer subunits that form filamentous actin
Placental structure
• Haemochorial --> Villi and outer surface of chorionic plate bathed in maternal blood • Fetus connected to placenta via umbilical cord • Placenta invasive to uterine tissue
What is the structure of intermediate filaments
• Have no unique structural basis 10nm
Describe neuronal migration control
• Inside out lamination • Mutations in the reelin gene cause defects in radial neuronal migration • Reeler mice have abnormal cortical layering
Extravillous trophoblast (EVT)
• Interstitial (iEVT) - regulate maternal immune cell tolerance • Endovascular (eEVT) - invade itno maternal blood vessels (break down lining of maternal spiral arteries) displace and form relining of blood vessels Highly invasive
Link stem cells with tumours e.g. in colon cancer
• Intestinal stem cells can act as the cells of origin of intestinal cancer • Tumours may be seeded and maintained by a small population of "cancer stem cells" - Starts with aberrant crypt --> polyp --> tumour
Explain what altered plane of division is
• Intrinsic mechanism • Altering the plane of division (via the mitotic spindle) can regulate asymmetrical cell division • Divides 2 cells in horizontal division, cell with apical bit will remain apical progenitor, cell on top will become another progenitor cell and divide and produce neurons
What do neurofilaments provide?
• Key structural support for axons, and regulate axon diameter (not length)
Desmin filaments support what cells?
• Key structural support in muscle cells, connecting sarcomeres (contractile units - actin/myosin) to the cytoskeleton
What does lamin do?
• Key structural support in nucleus, as well as involvement in transcriptional regulation, and remodeling of the nuclear envelope during mitosis/meiosis
How to repair cartilage?
• Limited repair capabilities as lacunae-bound chondrocytes have a limited migratory capacity to reach and repair damaged areas • There is no blood supply to hyaline cartilage so new matrix deposition is slow • Damaged hyaline cartilage is usually replaced by fibrocartilage scar tissue - i.e. loss of function
Syncytiotrophoblast
• Line villous • Multinucleated • Bathed in maternal blood - one giant multinucleated cell with continuous outer cell membrane
Yolk sac
• Lined by extraembryonic endoderm • Outside well vascularized extraembryonic mesoderm
Describe the process of lipolysis in human white adipocutes
• Lipolysis under control of sympathetic NS • Release NA acts at beta adrenoceptor • NA from nerve endings stimulates the cyclic AMP (cAMP) system, which activates hormone—sensitive lipase to hydrolyze the stored triglycerides to free fatty acids and glycerol
What immune cells are secreted? How are they regulated? What do they induce?
• Local Th1/Th2/Th17/Treg, M1/M2 balance • Regulated by trophoblast factors (HLA-G/C, CXCL/R) and trophoblast/decidual cytokines (IL10, IL4) • Induces decidual (d)NK and dTregs to be a distinct subset compared to systemic NK and Tregs
Function of the microtubules
• Make up the centrioles and form the spindle in dividing cells • Form flagella and cilia of a cell • Provide a pathway for intracellular movement of organelles, vesicles and proteins • Determine axonal length by extending neuronal growth cone
Describe placental exchange
• Maternal and fetal blood exchange occurs across the trophoblast cell layers of the placenta
The future of repair potential?
• Matrix of cartilage protects the cartilage from entry of lymphocytes or diffusion of immunoglobulins • Allows for transportation of cartilage from one individual to another without fear of tissue rejection - potential for stem cell-derived transplants
Give an example of abnormalities of neuronal development and what is it caused by?
• Microcephaly (small head) o Caused by: insufficient progenitor proliferation, impaired/premature neurogenesis, abnormal increase in ell death in progenitors or neurons
What happens in tangential migration?
• Migration from the ganglionic eminence into the cortex
Mouse models of neurofilament disorders exhibit phenotypes similar to what?
• Mouse models of neurofilament disorders exhibit phenotypes similar to motor neurone disease
What is neuronal migration?
• Neuroblasts generated from progenitor cells migrate along the process of the apical progenitor cell (radial glia) to the other part of the cortex → radial migration o Moving more towards the outside of the brain
Explain how patterning of the spinal cord occurs with Shh and BMP
• Notochord produces Shh (ventral side), BMP produced and are in the ectoderm (dorsal side) → results in different neurons produced at diff parts of spinal cord • Shh highest concentrations at the bottom and BMP at the top
Describe migration of microfilaments
• On mobile end of migrating cells, actin bundles project from the cell to form spike like filopodia • Between filopodia, there is lamopodia
What helps gyrus formation?
• Organisation and number of outer radial cells and processes • Outer radial glia are progenitor cells that lack an apical process (i.e. different to apical progenitor cells), they don't connect to ventricular surface, • Oblique orientation of outer radial glial processes may support gyrus formation
Describe the structure of lamellar bone
• Osteocytes are embedded between lamellae • Lamellar bone is highly organised and very strong
Developmental genes can be classified into a genetic hierarchy
• Pattern-forming genes • Master genes that specify cell lineages • Genes that regulate cell phenotype • Genes that code for tissue-specific functional products
Describe placental immunology
• Placental and decidual cells produce factors which modulate maternal immune cell phenotype/subset
Give examples of places cartilage is found
• Places found: compression/load is resisted, strength/structural integrity, degree of flexibility, unification of certain bones, articulation in synovial joints
Yolk sac in mammals
• Primordial germ cells arise in extraembryonic mesoderm near base of allantois (3rd week) • Become visible in lining of yolk sac • then migrate to the gonads. • Extraembryonic hematopoisis
Describe what happens in neurogenesis
• Proliferation in the neuroepithelium • Proliferation of the progenitor cells is via symmetrical division to produce more progenitor cells • Cells divide with nucleus next to the lumen (apical surface)
What is the function of intermediate filaments
• Provide mechanism stability • Take part in assembly of nuclear envelope • Support plasma
What happens in cortical lamination?
• Radial migration necessary • Neurons migrate to form the cortex in an inside-out manner - newer/younger cells further out (closer to outside of brain)
How does actin drive cell movement?
• Reversible assembly of actin drives cell movement → actin filament grows in the direction of cell movement, pushing plasma membrane forward
What is the process of neural induction?
• Signals converge on the middle region of the ectoderm and induce it to become neural tissue • Neural plate border (green) will form neural crest • Ectoderm produces signals Bmp and Wnt
Structure of WAT and size
• Spherical when isolated but polyhedral when closely packed • Each cell very large ~50-150 um in diameter • Contains one huge droplet of lipid that makes up 85% of cell's weight
M4 What is the role of cytoskeleton?
• Stabilises and protects the cell, determines its shape by providing mechanical scaffold
Microtubules size? made up of?
• Strongest and largest component of the cytoskeleton • Composed of alpha and beta-tubulin that forms long hollow cylinders
What produces human placental growth hormone? What is its role?
• Syncytiotrophoblast • Regulates maternal blood glucose levels
Describe what happens in neurulation
• The folding up of the neural plate to form the (continuous) neural tube • The brain and spinal cod maintain a tube-like structure (with a fluid filled space in the centre throughout life) • Tight cell filaments and actin combine to create folding • Neural tube cell and epidermal cells fuse over the top
What do the neurons become in tangential migration?
• These neurons develop into interneurons, in specific layers of the cortex
Placental villi role
• Villi floating in the intervillous space • Bathed in maternal blood • Outer surface of villi = lined by syncytiotrophoblast • *Role is to increase the surface area available for nutrient, gas and waste exchange between maternal and fetal blood*
What technique can be used in the four marker test to identify the levels of biomarker proteins in serum?
→ Maternal blood test