Anatomy Exam 2
growth factors list
Hedgehog proteins, WNT proteins, TGF-beta superfamily, neurotransmitters, FGF, RA
Atance question: what are EPF and hCG in regards to detecting pregnancy?
In humans, modern pregnancy tests detect human chorionic gonadotropin (hCG), which is secreted by the embryo and passes into the mother's urine, however hCG is NOT present UNTIL AFTER implantation, six to twelve days after fertilization (syncytiotrophoblast) Early pregnancy factor (EPF), an immunosuppressant protein, is secreted by the zygote and appears in maternal serum within 24 to 48 hours after fertilization It is believed to be the earlier possible marker of pregnancy; however, it may also be present in non-pregnant situations, thus rendering its effectiveness unclear at this point
Atance question: what are congenital hemangiomas?
- Due to excessive angiogenesis (vessels sprout from existing blood vessels, most commonly in somatic plate mesoderm) - Fully formed at birth - Most gradually degenerate/involute
Atance question: what are sacrococcygeal teratomas?
- From cellular remnants of the primitive streak - Most common congenital tumor in newborn - May be larger than fetus - Detected during prenatal ultrasound and usually require that delivery is via C-section
Atance question: what is the difference between paracrine and juxtacrine signalling?
- In paracrine signaling, cells interact with each other by secretion of diffusible protein growth factors (aka morphogens), which are often secreted in a manner that creates concentration gradients (leading away from the cells of origin) As such, there is a different fate for responding cells based solely on their distance from inducing cells - In juxtacrine signaling, cells interact with each other by physical contact, generally in three ways: A protein on a signaling cell binds to a receptor on a receiving cell (e.g., Notch signaling pathway) Integrin receptors on cell bind to extracellular matrix (ECM) proteins (e.g., collagen, fibronectin, laminin) Direct transmission of signals from one cell to another by gap junctions (important in epithelia)
RA signaling and retinoid disruption
- Like a steroid hormone, RA crosses the cell membrane, binds to its receptor in the cytoplasm, and the ligand-receptor complex travels to the nucleus where it binds the appropriate promoter to regulate expression of several hundred target genes - Crucial targets of retinoic acid receptors in development are the Hox genes, like the transcription factor MEIS1 (we will talk about these shortly)
vertebrae and rib formation
- Paraxial mesoderm (mesenchymal to epithelial) → somites (epithelial to mesenchymal) → sclerotome (bone) + dermamyotome (skin, muscle) - Genetically specified to form structures at a body level - Hox genes - Sclerotome cells migrate around neural tube and notochord and merge with opposing sclerotome - 4th week - sclerotomes divide transversely cranial/caudal halves - marked by von Ebner's fissure - Resegmentation - caudal/cranial fusion; Muscles - attached to 2 vertebrae across IV disc; Spinal nerves pass through - vertebral body, vertebral arch, spinous/transverse processes, ribs
spina bifida
- Rachischisis: failure of caudal neuropores - paralyzed completely from the point of the deficit caudally
molecular regulation of somite differentiation
- SHH secreted by Notochord induces somite to become sclerotome --> bone formation - BMP4 tells dorsal neural tube to secrete WNT --> MYF5 --> develops myotome and develop muscles eventually
day 8
- amniotic cavity appears (fluid in epiblast): epiblasts adjacent to cytotrophoblasts flatten --> amnioblasts; amnion surrounds amniotic cavity --> expands to enclose entire embryo in week 8
gastrulation
- bilaminar --> trilaminar - initiated at beginning of week 3 (forms ectoderm, mesoderm, and endoderm) - must have epithelial to mesenchymal cell transition (lose adhesion molecules to neighboring cells and become migratory)
day 9
- blastocyst (embryo) fully implanted in the endometrium - abembryonic pole: coagulation plug seals hole (some blood may leak causing women to think they have their periods) - hypoblast migrate to form primary yolk sac (aka primitive yolk sac, primary umbilical vesicle, Heuser's membrane, exocoelomic membrane) - primary yolk sac --> extraembryonic mesoderm - trophoblastic lacunae appear in syncytiotrophoblast; anastomose with sinusoids, filling with blood - maternal capillaries (from spiral arteries) expand to form sinusoids
day 6 (implantation)
- blastocyst captured by portion of trophoblast adjacent to embryoblast - endometrium undergoes transformation (stroma accumulate glycogen and lipids) to decidua (nutrition) - ectopic: implantation outside uterus in either uterine tubes or rectouterine pouch
neurulation
- brain and spinal cord form - notochord secretes inductive proteins that stimulate overlying ectoderm to invaginate - neuroectoderm now referred to as neural plate - invagination continues until lateral margins, neural folds, meet - non-neural surface ectoderm fuse and later give rise to epidermis of back - cells of neural folds detach just deep to surface ectoderm --> now neural crest cells - neural plate fuses to form neural tube --> precursor to brain and spinal cord
sacrococcygeal teratoma
- cellular remnants of primitive streak - tumor detected during prenatal ultrasound - requires C section delivery - usually benign
chondrification
- chondrification centers (cartilage development): condensed mesenchyme differentiate into chondroblasts - secrete extracellular matrix (collagenous fibrils, ground substance) - chondrocyte: chondroblast surrounds itself with ECM
day 15
- chorion (wall of chorionic cavity to become fetal membrane) has embryo, amniotic sac, and yolk sac suspended within it; contributes to placenta - blood vessels will develop, connecting stalk --> umbilical cord
week 12
- chorion + uterine wall --> no uterine cavity - chorion laeve is smooth (abembryonic villi have degenerated) - most of skeleton complete
day 12
- chorionic cavity (extraembryonic coelom) forms in extraembryonic mesoderm - primary yolk sac displaced by migrating hypoblast cells --> secondary/definitive yolk sac
week 6
- chorionic cavity and uterine cavity still present - interzone in the mesenchymal condensations preceding endochondral ossification - chondrification centers appear - paddle-shaped hands - facial tissue
days 1-3
- chromosomes in pronuclei replicate, mitosis occurs (deep furrow): cleavage occurs creating blastomeres; volume stays same given inelastic zona pellucida; early pregnancy factor secreted by zygote as immunosuppressant protein; morula creates inner and outer cell masses
day 13
- days 11-13: primary (chorionic) stem villi form (finger-like extensions of syncytiotrophoblast) with cytotrophoblast core grow into lacunae - coagulation plug has healed, but some bleeding occasionally occurs - may be confused with normal menstrual bleeding (inaccuracy in delivery dates)
notochord formation
- derived from mesoderm - forms along midline during gastrulation - induces formation of CNS - forms central portion of intervertebral discs (nucleus pulposus) - formed from prenotochordal cells by migrating through primitive node towards prechordal plate (signal migration to stop and form notochord)
birth defects by genetic factors
- during 1st 2 weeks when cell division is intense from a random mechanical error in cell division --> most spontaneously abort - numerical and structural chromosomal abnormalities affect 1 in 120 live born babies --> Down Syndrome as example - random DNA mutation unlikely to lead to improvement in development, most mutations are deleterious and some are lethal
mesenchyme and mesenchymal cells
- during gastrulation, epiblast cells ingress to produce mesoderm b/w epiblast and hypoblast - epithelial-to-mesenchymal cell transformation to ingress (epithelial cells are not migratory) - some cells go back (mesenchymal-to-epithelial) to displace hypoblast cells
rules of 2s (week 2)
- embryoblast into 2: epiblast and hypoblast - trophoblast gives 2 tissues: cytotrophoblast and syncytiotrophoblast - 2 yolk sacs: primary and secondary - 2 new cavities: amniotic and chorionic - extraembryonic mesoderm into 2 layers - primitive streak begins to form at end of week 2
day 5
- embryoblast: differentiates into scattered epiblast (amnion, embryo) and hypoblast cells (yolk sac, chorion, anterior visceral endoderm AVE cranial end) - bilaminar embryonic disc with dorsal-ventral axis - blastocyst hatches from ZP (due to mechanical pressure and lytic enzymes) --> can now increase in size
uteroplacental circulation
- embryonic/fetal blood enters placenta through pair of umbilical arteries --> sends branches into chorionic villi - fetal blood returns to embryo through one umbilical vein - maternal blood from (uterine) spiral arteries (from trophoblastic lacunae) enters intervillous spaces in endometrial veins - exchange occurs through barrier of villus wall
endodermal derivatives
- endodermal tube: epithelial lining of GI tract - endodermal bud: thyroid gland, parathyroid glands, epithelial lining of respiratory system (trachea and lungs), epithelial lining of urinary bladder, epithelial lining of urethra, liver, gallbladder, pancreas (accessory digestive organs)
surface ectoderm (ectodermal derivatives)
- epidermis - epidermal derivatives (hair, nails, sebaceous glands, sudoriferous sweat glands, arrector pilli mm, mammary glands)
day 16
- extraembryonic mesoderm penetrates primary stem villi --> secondary stem villi
week 7
- eyelids, philtrum, and digits begin forming - philtrum: indention above lips
anecephaly
- failure of cranial neuropores - no brain, brainstem still persists so can carry out basic functions for a short time - developing brain and spinal tube are exposed to amniotic fluid, leads to nervous tissue degeneration
ossification of cranium
- flat bones: intramembranous ossification - some irregular bones: endochondral ossification; cranial base - chondrocranium - fusion of several cartilages; undergo endochondral ossification - also face bones - pharyngeal arch cartilages - at birth, flat bones separated by sutures - sutures and fontanelles allow skull to grow for brain, and deform during delivery (parturition)
oropharyngeal and cloacal membrane
- forms after gastrulation - small regions fused ectoderm and endoderm - oropharyngeal membrane positioned at anterior 2/3 and posterior 1/3 of tongue, separates oral/nasal cavities - cloacal membrane is positioned over the coaca and typically degenerates during 7th week
primitive streak
- forms at end of 2nd week - Nodal secreted by cells in area to help establish - Nodal promotes expression of genes involved in proliferation and differentiation
days 6-12 (post implantation)
- hCG (human chorionic gonadotropin) secreted from embryo (pregnancy test detects) syncytiotrophoblast
ossification
- initial bone development day 33 week 12 - start with mesenchymal condensations that undergo either endochondral or intramembranous ossification
epithelium
- lines body cavities and surfaces - contains all 3 germ layers
bone-forming mesenchyme
- mesoderm: paraxial, intermediate, and lateral plate mesoderm - paraxial mesoderm: most of axial except cranial (neural crest mesenchyme) - lateral plate mesoderm: sternum, appendicular skeleton; sternal bars week 10; sternebrae - 4 cartilaginous precursors
day 4
- morula reaches uterus - blastocyst cavity (blastocoel) formed: uterine fluid penetrates ZP in 32 cell morula - embryoblast: inner cells (embryo and structures) - trophoblast: outer cells (placenta) - blastocyst is formed with embryonic and abembryonic poles
neurulation and neuropores
- neural folds initially meet in cervical region of embryo ~ day 22 - occurs bidirectionally cranially and caudally - cranial close at day 25 - caudal neuropores close at day 28 - failure of neuropores lead to neural tube defects
intervertebral disc formation
- outer annulus fibrosis: from cells in von Ebner's fissure - inner nucleus pulposus - cells within the notochord differentiate - notochord enclosed by vertebral bodies/degenerates/disappears - week 5: vertebrae are mesenchymal - week 6: chondrification centers create cartilaginous vertebrae - week 7: primary ossification centers; ossify vertebrae (secondary at puberty)
pharyngeal clefts, arches, and pouches (CAP)
- p. arches consist of clumps of tissue located along lateral walls of GI tract in p. region (PA 1, 2, 3, 4, 6) - PA: outer ectodermal lining, inner endodermal lining, core of mesenchyme containing a developing nerve, artery, and cartilage - p. cleft are external grooves b/w PA - p. pouches are internal grooves b/w PA - p. membranes are points of contact of ectoderm and endoderm
week 4
- portion of yolk sac endoderm --> midgut, stays attached by vitelline duct - if vitelline duct fails to degenerate --> Meckel diverticulum or fistula from small intestine to umbilicus - embryo blood forms - initial formation of bone - resegmentation --> Sclerotomes divide --> von Ebner's fissure - oropharyngeal membrane degenerates - cranial neuropores close day 25 - caudal neuropores close day 28 - pharyngeal arches/clefts form cranio-caudally - limb buds, cardiac prominence
formation of intraembryonic coelom
- presence of vacuoles within lateral plate mesoderm initiate formation of the intraembryonic coelom - result of lateral folding; this space is incorporated into the ventral aspect of the embryo - vacuole formation and intraembryonic coelom formation separate the lateral plate mesoderm into somatic and splanchnic mesoderm (dorsal = somatic; ventral = splanchnic)
week 3
- primordial germ cells in endodermal lining of yolk sac --> abdomen - blood development initiated in yolk sac - develops its own circulation - chorionic blood vessels grown in mesoderm of secondary stem villi --> tertiary stem villi; begin connecting sinusoids to embryo blood vessels to establish uteroplacental circulation to exchange gases and metabolites - gastrulation begins (oropharyngeal and cloacal membrane forms)
embryonic folding
- provides basic body cylinder - occurs during 4th week - lateral and cranial caudal folding
neural crest (ectodermal derivatives)
- sensory neurons of PNS - medulla (chromaffin cells) of adrenal gland - enteric neurons - sympathetic ganglia and neurons - pia mater and arachnoid mater (leptomeninges) - membranous interventricular septum of heart - dermis and hypodermis of head (adipocytes) - bones/cartilage of head - odontoblasts - melanocytes
placental membrane or barrier
- separates maternal and embryonic blood (no mixing usually) - offers nutrition and protection - 4 layers: 1. endothelial lining of chorionic capillaries 2. connective tissue (villus core) 3. cytotrophoblast 4. syncytiotrophoblast
birth defects
- structural, behavioral, functional, or metabolic disorder present at birth - most likely to arise during organogenesis (week 3-8); 1st 2 weeks = lethal defects; after 8 weeks = intellectual and learning disabilities - can be genetic and/or environmental
principles of teratogenesis
- susceptibility depends on genetic make up of embryo/fetus and mother - dependent on dose and duration of exposure to teratogen - stage of development can impact effects (most sensitive during weeks 3-8)
week 8
- trilaminar disk (ectoderm, mesoderm, endoderm) --> humanoid 3D structure - fetal membranes pushed out - uterus filled - amnion + chorion (laeve) --> amniochorionic membrane (ruptures in labor) --> no chorionic cavity - villi on embryonic pole have been growing/expanding --> chorion frondosum - villi on abembryonic pole degenerate - decidua (decidua basalis, decidua capsilaris, decidua parietalis) --> maternal contribution to placenta - embryonic joints resemble adult ones - genitalia recognizable - digits fully formed
day 6 continued
- trophoblast (adjacent to embryoblast) and endometrium --> shed membranes and fuse to form syncytiotrophoblast (penetrates endometrium and pulls embryo into uterine wall) - rest of cells: cytotrophoblast
Atance question: know neural tube defects
1. Anencephaly literally means "no brain", however, the brainstem typically persists allowing the infant to carry out basic functions for a short while Because the neural tube fails to close properly, the developing brain and spinal cord are exposed to amniotic fluid that surrounds the fetus in the womb This exposure causes the nervous tissue to degenerate. The cause of anencephaly is disputed; however, it is known that maternal intake of adequate amounts of folate reduces the likelihood. Incidence is 1/1000 2. Rachischisis: Failure of the caudal neuropore to close results in a form of spina bifida (referring to the 2 processes of an incompletely formed vertebrae), specifically a form known as rachischisis This term means "split spine" and is often seen with anencephaly. The infant will be paralyzed completely from the point of the deficit caudally. 3. Complete NT failure
stages of development
1. Pre-Embryonic Development: 0-2 weeks; increase cell # 2. Embryonic Period: 3-8 weeks; morphological changes; most susceptible to teratogens 3. Fetal Period: 9 weeks - birth
embryonic axes
1. anterior-posterior (cranial-caudal): indicated by orientation of the primitive node and anterior visceral endoderm (AVE) 2. dorsal-ventral: indicated by location of primitive streak; bone morphogenic protein (BMP4) plays a role 3. right-left: FGF8 and Nodal play roles; deduced by other 2 axes
mesodermal derivatives
1. axial: notochord, induce neural tube formation, differentiate into nucleus pulposus of IV disc 2. paraxial: form somites --> sclerotome/inner (axial skeleton), dermatome/outer (dermis of dorsal and lateral body), and myotome/middle (skeletal muscle) 3. intermediate: much of urinary system 4. lateral plate: somatic (dermis of ventrolateral body wall, hypodermis, and all skeletal components of limbs; smaller, more peripheral blood vessels) and splanchnic (smooth muscle and CT of organs and most of heart; larger, more central blood vessels)
fertilization (day 0)
1. capacitated sperm pass through corona radiata 2. sperm bind ZP3 causing acrosomal rxn 3. fusion into zygote: metabolic activation into egg; prevention of polyspermy through cortical granules hydrolyzing ZP3 receptors and modifying oocyte; chromosomal sex determination
pre-fertilization
1. gametogenesis 2. sperm undergoes capacitation (1-10 hours): cholesterol removed from membrane; membrane glycoproteins removed to uncover binding proteins --> ZP3; mediated by uterine/uterine tube secretions
3 types of cartilage
1. hyaline (joints, skeleton) 2. fibrocartilage (intervertebral discs) 3. elastic cartilage (auricle of ear)
4 types of teratogens
1. infectious 2. physical 3. chemical 4. hormones
embryology
1st 8 weeks of development specifically; more generally it refers to conception to birth
Atance question: how many sclerotomes contribute to the formation of a vertebra?
Resegmentation resets myotome and vertebral levels In the 4th week, the sclerotomes divide transversely into a loosely packed cranial half and a densely packed caudal half; this division is marked by von Ebner's fissure Resegmentation occurs when the caudal half of one sclerotome fuses with the cranial half of an adjacent sclerotome Thus, each vertebra is formed from four sclerotomes - the caudal halves of two sclerotomes (one on each side of the neural tube) and the cranial halves Resegmentation has TWO important rules: Muscles derived from the myotome region of each somite become attached to two adjacent vertebrae across an IV disc and can therefore move the vertebral column Spinal nerves pass through cranial halves of sclerotomes, which are more loosely packed; however, after the vertebral column ossifies, spinal nerves pass in-between vertebrae
birth defects by environmental factors
Rubella --> from sedative thalidomide main point: drugs can cross placenta and produce birth defects
Atance question: what is the purpose and process behind capacitation?
Sperm must undergo capacitation before they can fertilize an egg: Sperm can reach the uterine tube in as little as 5 min after ejaculation but can't fertilize the egg for several hours While migrating, they have to undergo capacitation -> a 1 to 10 hour process with two main outcomes: A cholesterol coat is removed from the portion of sperm membrane covering the acrosome, in preparation for the release of enzymes from the acrosome (acrosomal reaction) -> the cholesterol coat is added in the testes as a means of preventing premature acrosome reaction, which would be counterproductive to fertilization (and could damage male ducts) Sperm membrane glycoproteins (acquired in the epididymis) are removed in order to uncover binding proteins, which will interact with ZP3 (receptor protein of the zona pellucida of the oocyte) Process is mediated by uterine and uterine tube secretions-> sperm can also be artificially capacitated during in vitro so contact with the female reproductive tract is not required
Atance question: what is the physiology of a woman's "water breaking"?
The decidua and the chorion contribute to the placenta The decidua consists of decidua basalis, decidua capsularis, and decidua parietalis The decidua basalis represents the maternal contribution to the placenta In early weeks of development, villi cover the entire surface of the chorion, but as pregnancy advances, villi on the embryonic pole continue to grow and expand, giving ride to the chorion frondosum Villi on the abembryonic pole degenerate, and by the third month, this side of the chorion, now known as the chorion laeve, is smooth The amnion and chorion laeve fuse to form the amniochorionic membrane, which obliterates the chorionic cavity It is this membrane that ruptures during labor (breaking of water)
Atance question: what is an atavistic tail a result of?
True human tails are rare but do occur when embryonic tail regression is incomplete. The tail consists of epidermis, dermis, hypodermis and striated muscle (in some cases causing it to move). Related to paraxial mesoderm
tutor question: which of the following events is involved in the cleavage of the zygote during week 1 of development?
a decrease in size of blastomeres --> cleavage is a series of mitotic divisions by which the large amount of zygote cytoplasm is successively partitioned among the newly formed blastomeres; although the # of blastomeres increases during cleavage, the size of individual blastomeres decreases until they resemble adult cells in size
teratogens
agents, such as chemicals and viruses, that can reach the embryo or fetus during prenatal development and cause harm
post-natal
birth to adulthood
TGF-beta superfamily
bone formation and involved in regulating cell division, cell death, and cell migration among other functions
endochondral ossification
differentiate into chondrocytes --> cartilage framework --> osteoprogenitor cells --> osteoblasts --> replace cartilage with bone tissue
malformation
direct result of abnormal development; ex: neural tube defects
nerve
ectoderm
tutor question: which germ layers are present at the end of week 3 of development (day 21)?
ectoderm, mesoderm, and endoderm (remember 2 for 2 weeks and 3 for 3 weeks)
mesenchyme
embryonic connective tissue; gives rise to adult CT and to muscle; mostly from mesoderm, some neural crest cells from ectoderm become mesenchymal; mesenchymal cells (migrate and differentiate) and extracellular matrix
process of signaling
extracellular signal --> intracellular signaling pathway --> activation or repression of transcription factor --> possible effects
developmental biology/anatomy
fertilization to adulthood
Atance question: lack of a philtrum occurs in what scenario?
fetal alcohol syndrome; usually formed around week 7; lack of notch or indentation above upper lip
interzone
first event of joint formation; in mesenchymal condensations; differentiates into fibroblasts --> joint structures; fibrous (sutures) and cartilaginous joints differentiates very little; synovial joint into articular hyaline cartilage
dysmorphogenesis
formation of abnormal tissue; malformations and deformations
tutor question: the first indication of gastrulation in the embryo is ____
formation of the primitive streak
tutor question: where does the blastocyst normally implant?
functional layer of endometrium
tutor question: which process establishes the 3 definitive germ layers?
gastrulation
deformation
indirect result of an abnormal development; ex: club feet if insufficient amniotic fluid forms (oligohydramnios) = mechanical constraints
FGF and RA
limb formation (see retinoid)
Hedgehog proteins
master morphogens for widespread role of many organs; involved in formation of many organs including vasculature, limbs, heart, lungs, gut, pancreas, kidneys, bladder, hair follicles, teeth, ears, eyes, taste buds
fetology
maturation for functioning organ systems; 9 weeks to birth
connective tissue and muscle
mesoderm
WNT proteins
notable for lengthening embryo and neural tube during gastrulation and neurulation
intramembranous ossification
organize into a sheet and forms ossification centers (directly differentiate into osteoprogenitor/osteoblasts/bone tissue); spicules of bone form continuous later --> flat bones of skull and most of clavicle
Atance question: conjoined twins are a result of what?
overexpression of molecules along primitive streak
juxtacrine signaling
physical contact needed 1. protein on signaling cell binds to a receptor on receiving cell (Notch signaling pathway) 2. integrin receptors on cell bind to ECM proteins (collagen, fibronectin, laminin) 3. direct transmission of signals from one cell to another by gap junctions (important in epithelia)
morphogenesis
process by which an organism takes shape and the differentiated cells occupy their appropriate locations; structural changes of an organ/organism; leads to differentiation
gametogenesis
production of gametes; 2 divisions; Meiosis I and II; sperm and egg results; 4N (92 chromatids) --> 2N (46 chromosomes) --> 1N (23 chromosomes)
bone
refers to an organ or a tissue; organ (bone) vs. tissue (osseous tissue)
Hox genes
series of genes that controls the differentiation of cells and tissues in an embryo; important for patterning; mutations can arise leading to several problems
neurotransmitters as growth factors
serotonin, GABA, epinephrine, and norepinephrine
tutor question: A 26-year-old female presents for annual wellness exam, and would like to start trying to conceive a child, with no significant medical history and no other medications. She has been using oral contraceptive pills and you recommend she discontinues them. Patient presents again to clinic 2 months later after a positive home pregnancy test. Confirmatory urine pregnancy test in the office is positive. The tissue that produces the hormone measured in this test is the:
syncytiotrophoblast of the placenta; hCG is secreted into maternal circulation after implantation (6-12 days after ovulation)
tutor question: A pediatrician is called to the newborn nursery to evaluate a baby with dysmorphic features. Physical examination reveals hypertelorism, cleft palate, and microcephaly. A heart murmur is detected, and ultrasonography confirms the presence of a ventricular septal defect. The mother, is a teenager who took a retinoid medication for severe pustular acne during pregnancy. The medication most likely exerted teratogenic effects on the newborn during what week of development?
week 6; period of highest embryonic vulnerability to teratogens is during weeks 3-8 after fertilization
Atance question: how are embryonic axes established as early as week 1?
~ Day 5, Embryoblast begins differentiating into future embryonic and extra-embryonic tissues: Cells of the embryoblast begin differentiating into scattered epiblast cells and hypoblast cells Within a day (and even before implantation), these cells organize to form a layer of epiblast cells and a layer of hypoblast cells The resulting two-layered embryoblast is called the bilaminar embryonic disc (or bilaminar blastoderm), which establishes two very important parameters: Epiblast cells give rise to the amnion and all tissues of the embryo proper, while hypoblast cells give rise to yolk sac and chorion, primarily Hypoblast cells develop ventral to the epiblast, and this relationship persists, thus establishing a very early dorsal-ventral axis for the embryo; moreover, some of the hypoblast cells are destined to form anterior visceral endoderm (AVE), which is responsible for specifying the cranial end of the embryo
external morphology of embryo
- 4th week: p. arches form cranio-caudally; p. cleft form cranio-caudally; eye, ear and nasal primordia begin to form (placodes); cardiac prominence; limb bud - 5th week: hepatic prominence; all pharyngeal arches and clefts have formed - 6th week: paddle shaped hands have formed; facial tissue beginning to converge - 7th week: eyelids, philtrum (not in FAS babies), digits begin to form - 8th week: external genitalia become recognizable; digits completely formed
Atance question: Understand chorionic stem villi, the placental membrane (barrier), and the principles of uteroplacental circulation
Chorionic blood vessels connect embryonic and maternal circulations: ~Day 16, the extraembryonic mesoderm associated with the cytotrophoblast penetrates the core of the primary stem villi, transforming them into secondary chorionic stem villi By the end of week 3, chorionic blood vessels have grown within the mesoderm of the secondary stem villi. With the presence of blood vessels, these villi are now called tertiary (chorionic) stem villi Blood vessels of the tertiary stem villi begin connecting to blood vessels forming in the embryo proper This establishes a working uteroplacental circulation, as sinusoids are connected by chorionic blood vessels to embryonic blood vessels The Placental membrane prevents mixing of embryonic and maternal blood The placental membrane, which separates maternal and embryonic blood, is composed of four layers: The endothelial lining of chorionic capillaries The connective tissue in the villus core The cytotrophoblast The syncytiotrophoblast Sometimes called the placental barrier, the placental membrane is not a true barrier, as many substances pass through it freely Nonetheless, the membrane is considered important in terms of regulating delivery of essential nutrients, removing waste as well as protecting the embryo/fetus from potentially noxious substances Normally, there is no mixing of maternal and embryonic blood, however, small numbers of embryonic blood cells occasionally escape across microscopic defects in the placental membrane Uteroplacental Circulation Embryonic/fetal blood enters the placenta through a pair of umbilical arteries, which send branches into the chorionic villi, where (fetal) capillary networks form: fetal blood returns to the embryo in a single umbilical vein Maternal blood from (uterine) spiral arteries enters the intervillous spaces (which arose from the trophoblastic lacunae) Maternal blood leaves the intervillous spaces in endometrial veins Exchange of substances between fetal blood and maternal blood occurs across the barrier formed by the villus wall This placental barrier does not exclude many potentially dangerous agents such as alcohol, drugs, nicotine, etc...
tutor question: A 12-year-old female presents to pediatrician with complaint of lower back pain. History reveals intermittent lower back pain, sometimes coupled with pain, weakness, or numbness in either posterior leg. Physical examination reveals a tuft of hair on the lower back, and mild scoliosis in the thoracic and lumbar region of the vertebral column. CT imaging reveals incomplete vertebral arches from L3-L5. However, there is no herniation of the meninges or spinal cord. Failure of which developmental event is most likely for this clinical presentation?
caudal neuropore closure; Neurulation begins in week 3 of embryonic development as part of the ectoderm first differentiates into neuroectoderm, then a neural plate, then a neural groove, and finally internalized neural tube.The neural tube will form the CNS (brain, spinal cord). The cranial and caudal neuropores (openings) of the neural tube typically close during the 4th week, isolating the developing CNS from the surrounding amniotic fluid. Failure of the caudal neuropore to close leads to incomplete formation of vertebral arches, causing range of spina bifida outcomes.
paracrine signaling
cells interact with each other by secreting growth factors
