BIOL 3040
What is the Central Dogma of Life?
(?) cell theory - all cells come from other cells each step you get more committed to what you're going to become
Which receptors drive dorsal into the nuclei, and and where are they found?
(overexpression of dorsal) receptor that drives dorsal into the nuclei - tolike receptor and spatzle - if it's not just on the ventral side, but everywhere dorsal in drosophila is kind of like a morphogen
Recessive mutation
++ = wild type, normal wings +- = normal wings -- = vestigial wings
Semidominant mutation
++ = wildtype, normal +T = deformed tail TT = embryonic lethal (abnormal posterior mesoderm)
What happens when Wnt is present?
-GSK3-beta is inhibited by Wnt binding to receptor and Beta-catenin levels increase -Beta-catenin goes to the nucleus and activates genes
4 Easy Steps to Building an Organism
1) Pattern Forming 2) Morphogenesis 3) Cell Differentiation 4) Growth
21 rules of life (and DB)
1. Your fate is determined by how much you listen to your mother versus your neighbors. 2. You don't have to be fully mature to influence your neighbors. 3. Listening is as important as talking. 4. Relationships matter! 5. Context matters. 6. Timing is everything. 7. And so is location. 8. The units of construction are not necessarily the units of the adult. 9. Think globally, but use local contractors. 10. No one influences everything. 11. Life is a series of pushes and pulls. 12. Reciprocal interactions are THE rule. 13. Two negatives DO equal a positive. 14. Don't digest your tail until you've built your hindlimbs. 15. Powerful entities must be regulated. 16. Redundancy is important. 17. There is strength in community. 18. Redundancy is important! 19. The whole is greater than the sum of its parts. 20. One's function changes with time. 21. There are multiple paths to the same end. (Redundancy is REALLY important!)
How long until Drosophila goes through gastrulation (embryo before hatching) and how long to does it take overall to hatch?
10 hrs, 1 day
What is the correct dorso-ventral arrangement seen in a cross-section of Drosophila embryo? How do these cell compartments arise? (What is the mechanism?)
Amnioserosa, dorsal ectoderm, ventral ectoderm, mesoderm
If cells from the animal pole of a frog blastula (animal cap cells) are placed into contact with cells from the vegetal hemisphere, after removing the cells fated to form mesoderm, what is the result?
Animal cap cells are induced to form mesodermal derivatives.
What happens if you take animal and vegetal cells out of an embryo, and put them in separate dishes?
Animal pole becomes ectoderm Vegetal pole becomes endoderm Example of specification; don't need neighbors to become cell types Before zygotic transcription Likely maternal determinants that specify endo/ectoderm from the beginning
IF you delete ___, everything turns into neural tissue (no skin).
Anywhere you have neural tissue, you don't have skin (seen in lower left box) If you delete BMP, everything turns into neural tissue (no skin) BMP has to be kept out of the way to create neural tissue The default state of the ectoderm is to become neural tissue; the organizer ensures that one section of the ectoderm stays neural by keeping BMP out of the region (with chordin, noggin, follistatin) BMP drives the ectoderm to become epidermis; inhibitor of neural tissue > Inhibit the inhibitor (BMP) in order to stay in default state
As long as _________________, you will get mesodermal tissue
As long as ecto/endoderm are near each other, you will get mesodermal tissue
Important to remember that it's a center on the _____ side that secretes b-catenin
B catenin
What happens when Wnt is absent?
B catenin is degraded and gene is not transcribed no Wnt at all: then organizer won't develop, dorsal style mutant
What happens when B catenin is injected into the ventral vegetal region of a cell?
B catenin is normally on the dorsal side results in twinned embryo with duplicated axis, i.e. Wnt signaling drives organizer formation
What are the human equivalents of dorsal, dpp and tld?
BMP, Chordin and Noggin
What happens if you split a frog embryo before gastrulation?
Before gastrulation, if you split a frog embryo, you still get 2 normal tadpoles (you just need the organizer, i.e. split in half along the organizer)
How does the activity of the shield region of the zebrafish compare with the activity of the Spemann organizer of the amphibian embryo?
Both have organizer activity. Include details of transplantation experiments, contribution of grafted tissue, changes in organizer activity over time.
Complexity of development is due to the inherent __________ of ___________
Complexity of development is due to the inherent complexity of the cells themselves
Which technique is commonly used for gene knock-out in mice? How does it work?
Cre/loxP system (?) mutating embryonic stem cells in vitro, ES cells come from the inner cell mass of a blastocyst, and are injected into the cavity of an early blastocyst to become incorporated into that cell's inner cell mass. The mouse will then become a chimera of the two genotypes.
Although the vertebrate body plan outwardly displays a mirror-image symmetry with regard to left and right, the internal organs are not symmetrical. How does this left-right asymmetry develop?
Differential release of Ca2+ ions on the left side leads to expression of Nodal and Pitx2 on the left. a theory for how this symmetry develops is that there is an initial asymmetry at the molecular level that impacts the multicellular level. Ciliary activity is important in creating this patterning, and Nodal is a left patterning protein involved.
Developmental genes act hierarchically during pattern formation, first defining broad regions, which are secondarily refined to form a larger number of smaller regions. Summarize how this general principle is illustrated by early Drosophila development.
Discuss maternal products that set up the axis, how these lead to gap genes, and how the combination leads to segmentation. This is shown through early Drosophila development, because at the start bicoid and caudal determine which side of the egg is anterior or posterior. At a specific bicoid threshold, hunchback is activated, which in turn activates other gap genes. These gap genes interact with one another to localize themselves properly. This shows that there is a gene hierarchy that first defines broader areas before specifying smaller regions.
An early event in axis formation is the accumulation of the transcription factor β-catenin in the nuclei on one side of the Xenopus embryo. Which side of the embryo does this specify? Describe briefly how the actions of β-catenin lead to specification of the Spemann Organizer.
Dorsal side; include expression of siamois and formation of Nieuwkoop center, Nodal signaling, expression of goosecoid.
Segmentation process
Egg --> Gap genes --> Pair-rule genes --> (Segment Polarity) --> Homeotic
Everything after gastrulation is _______ transcription; no longer depend on _______________
Everything after gastrulation is zygotic transcription; no longer depend on maternal determinants
All vertebrates share certain features. What are those features? And why are they the same
Features seen in all embryos shown in Figure 3.2 include head with eye, tail, and somites. Other common features not seen externally include dorsal neural tube and notochord, heart and ventral gut. Limb buds are apparent in the chick, mouse and human embryos. All vertebrates have a similar body plan including the vertebrae column, spinal cord and a skull that encloses the head and brain. They are all the same because they share similar patterning during gastrulation.
What are the basic principles of vertebrate development?
Fertilization Cleavage Gastrulation Neurulation Relationship to Mother
What is forward genetics? Reverse genetics? Please list an example of each.
Forward genetics (or a forward genetic screen) is an approach used to identify genes (or set of genes) responsible for a particular phenotype of an organism. Reverse genetics (or a reverse genetic screen), on the other hand, analyzes the phenotype of an organism following the disruption of a known gene.
Where do germ cells come from?
Gastrula
What is the name of the process in which the three germ layers are formed? Describe it.
Gastrulation is when cells move around each other to form three germ layers that eventually becomes the ectoderm on the outside, while the mesoderm and endoderm move inside to create muscles, skeletal system, and the gut (etc.)
How does gastrulation work to create A/P patterning?
Gastrulation works on D/V axis and makes A/P patterning Dorsal area becomes head (anterior); ventral becomes tail (posterior) Organizer is always in the same position became when cells move during gastrulation, they become the organizer as they reach that spot
inducible genes
Genes not normally expressed but can be in response to external stimuli (e.g. hormone).
developmental regulatory genes
Genes specific to certain stages during growth and development of a person
cell type specific genes
Genes that are turned "on" in each cell that give a cell its special properties and function
2012 Nobel Peace Prize
Gurdon - genetic equivalence and differential gene expression replaced frog egg nucleus with specialized tadpole nucleus --> developed into a normal tadpole (cloning) so genes are not permanently silenced or discarded Yamanaka - induced pluripotent stem cells (pluripotent - capable of giving rise to several different cell types) identified four transcription factors(?) can make stem cells out of muscle tissue induced pluripotent stem cells = iPS ES cells are pluripotent iPS are pluripotent, induced from unipotent
How does Henson's node move throughout development?
Hensen's node moves posterior to anterior through gastrulation When it reaches the anterior part of the embryo, it starts to move back to the posterior As it does this, it secretes signals to allow somites to form
Relative to the primitive streak and Henson's node, how does somite formation in the chick embryo occur?
In chicks, Henson's node is similar to the Spemann organizer, at is at the end of the primitive streak. The primitive streak is where most mesoderm patterning happens (but not dorsal mesodermal patterning), and Henson's node leads to the prechordal plate and notochord.
Pattern formation is a central process in the study of developmental biology. Describe three examples of pattern formation and explain what "patterns" are generated.
Laying down the body plan, development of the limb, and arrangement of neurons in the nervous system. You should be able to give more details as you progress through the book. Could also include the French flag model.
mitosis vs. meiosis
Mitosis: one division forming 2 identical cells (clones) (2n); Meiosis: two divisions forming 4 genetically different cells (n)
What doles the "default model" for neural tissue formation state?
Neurectoderm formation is inhibited by the BMP proteins present throughout the early embryo, and this inhibition is relieved by BMP antagonists from the organizer, such as chordin
Key to Development
No developmental process can be attributed to a single gene or protein no single cell, process, or gene drives anything development is cell-cell interactions, developing an organism as a whole not just building hearts and tissue on their own redundancy - two negatives do make a positive feedback inhibition development is never a straight line
symmetric cell division
Results in two daughter cells that are similar, either self- renewal (the same as the mother cell) or self-differentiation (two differentiated cell)
What is the mechanism by which cells fated to be mesoderm form in the marginal zone of the Xenopus embryo?
Secreted signals of the TGF- family are released by the cells of the vegetal region and act on the adjacent cells of the marginal zone to instruct them to adopt a mesodermal fate.
What prevents dpp from spreading ventrally?
Sog
How do some maternal determinants work as inhibitors?
Some of the maternal determinants are inhibitors to transcription; purposely silence transcription of genome until correct time In every cell division, the inhibitor dilutes in half Eventually, inhibitor gets less and less per cell goes below threshold; zygotic transcription is no longer inhibited
Where are chordin and noggin expressed?
Spemann's organizer --> inhibitors to bmp4 signaling
The ____ pole is on the top of the blastula, the ____ pole is at the bottom.
The animal pole is on the top of the blastula, the vegetal pole is at the bottom. (become dorsal and ventral)
All cells in an organism contain the same genes; however, it contains different types of cells. How is this paradox of "genetic equivalence" resolved by the concept of "differential gene expression"?
The control of gene expression is central to development as the genes that a cell expresses determine the proteins that it makes. Differentiated cells express different subsets of genes and therefore make different proteins that enable them to carry out their specialized functions.
A fate map of a Xenopus blastula, just before gastrulation begins, shows (Figure 4.9) that the top portion of the embryo will become ectoderm (skin and nerve), the central portion will become mesoderm (bone, muscle, and blood), and the lowest portion will become endoderm (gut). How is it that the endoderm and mesoderm, shown on the outside in the fate map, end up on the inside in the embryo after gastrulation?
The endodermal cells begin first to move into the embryo through the blastopore, displacing the blastocoel and forming a gut; as gastrulation proceeds, the blastopore spreads sideways and the mesoderm follows the endoderm in, ending up between the endoderm and the ectoderm.
What is the difference between "fate" and "specification"? Give definitions of each and explain how they're different.
The fate of a cell is determined by labeling that cell and following it during normal development, whereas the specification state of a cell is determined by culturing a cell in an artificial medium and observing what tissues form from it.
In Figure 1.23, when the presumptive eye region from a gastrula is grafted into the trunk region of another neurula, it develops to somitic tissue; whereas transplant from eye region of later stage neurula develops as an eye-like structure in host embryo. What does this experiment illustrate?
The graft from neurula stage is determined.
What property of the mammalian embryo permits the production of chimeric mice?
The inner cell mass is highly regulative, so that extra cells derived from the inner cell mass of a different embryo are incorporated without causing defects.
Distinguish between the notochord, the spinal cord, and the vertebral column and describe the relationships between the following structures: neural plate, neural folds, neural tube and neural crest.
The notochord is a mesoderm structure that is eventually part of the vertebral column. The spinal chord is part of the central nervous system, and is protected by the vertebral column, which is part of the skeletal system. The neural plate is part of the anterior ectoderm, and during neurulation, the neural folds come up at the edges of the neural plate and bond to create the neural tube. Neural crest cells come from the neural plate and proliferate to different areas of the body to create nerve systems and other structures. See also glossary; spinal cord develops from the neural tube in the body. Use diagrams for the second part of the answer.
fertilization
The posterior marginal zone in a chick embryo becomes the primitive streak, which is responsible for patterning of the mesoderm. It is equivalent to the Niuewkoop center in frogs, and is significant to chick development because it is an important part in the formation of cell layers.
What is the posterior marginal zone of the chick embryo? What is its significance to chick development? Compare it to other organizer structures in other organisms.
The posterior marginal zone in a chick embryo is like the Niuewkoop center in frogs. It becomes the primitive streak and is the posterior end of the embryo, and is responsible for patterning of the mesoderm. See also definition in glossary. Position in which primitive streak arises marking posterior end of embryo.
What is preimplantation genetic diagnosis (PGD)?
The surgical opening and inspection of an artificially fertilised embryo for a selected gene mutation - if it doesn't have the mutation, it is inserted into the uterus
What do Hox genes do?
They control the roles of each segment, the differentiation of cells and tissues in the embryo
The specification of the 14 parasegments along the anterior-posterior axis depends on precise spatial expression of the pair-rule genes. Pair-rule gene expression depends in turn on the gap genes. Using the second stripe of even-skipped (eve) expression as a model, summarize the interactions that lead to proper expression of Bicoid, Hunchback, Kruppel and Giant. In particular, describe how the anterior border of Kruppel is set and how this boundary sets the posterior border of eve stripe 2 expression.
This will require an understanding of, and an introduction to, transcription and how it is possible to define spatial domains of gene expression through combinations of transcription factors as determined by their binding sites. You should look up the details of eve stripe 2 if you need to. Bicoid and Hunchback activate eve. Kruppel and Giant define eve boundaries; when Kruppel and Giant levels are high, eve is inhibited. The anterior border of Kruppel is set by a concentration threshold of Hunchback. This boundary is the posterior border of eve stripe 2 expression due to a threshold concentration of Kruppel expression. The anterior edge of eve is at a threshold for Giant concentration.
What is VegT?
VegT: maternal determinant (gene) on vegetal pole that makes endoderm Also makes Nodals --> proteins that tell cells above it to become mesoderm Mesoderm development is blocked from animal pole by ectoderm
What are three ways in which inducing signals can be transmitted in a developing embryo? In what circumstance would an inducing signal be a morphogen?
Via secreted molecules - usually proteins that bind to receptors on responding cells, via direct cell‐cell contact, via passage of small molecules through gap junctions - see Figure 1.25. For morphogen: see definition in glossary.
What questions to answer when reading a scientific paper
What is the main hypothesis of the paper? Do the results support the hypothesis? What conclusions are drawn from the study? Do you believe the authors? If not, what else would you want to see?
Where is Wnt distributed?
Wnt is on the dorsal side
How does Wnt interact with the Spemann's organizer?
Wnt is used to develop Spemann's organizer, but once Spemann's organizer is determined, it blocks everything (including Wnt) out
Patterning of the Xenopus mesoderm along the dorso-ventral axis involves an antagonistic relationship between chordin and BMP-4. Is there an analogy here to dorso-ventral patterning in the Drosophila embryo? If yes, how?
Yes, the Drosophila homolog of BMP-4, Decapentaplegic (Dpp), is antagonized by the Drosophila homolog of chordin, short gastrulation (Sog), in patterning of the dorso-ventral axis.
hat are some of the features that would make an animal model species a good 'model organism' for the student of development? For example, what features make a zebrafish an attractive model for development compared to a mouse? In contrast, what advantages does the mouse offer over the zebrafish?
You will find the information to answer this question summarized in Figures 3.34 and 3.38. A good model organism shares relevant similarities with other organisms and has life cycles that are useful for the study. A zebrafish is a good model organism because of its short life cycle and transparency of the embryo. on the other hand, a mouse is a good model organism because of its short life cycle (for a mammal) and because of genomic and transgenic capabilities.
What is a homeotic gene?
a class of regulatory genes that SPECIFY & DIVERSIFY the identity of body parts and regions in an animal embryo. Mutations in these genes can transform one body part into another homeotic genes - homeo box - bind DNA really unique transcription factors homeotic - if you mutate one of them, you don't lose a tissue, it becomes something else interpreting different levels of homeotic genes (don't need to know names, just need to know how to interpret it)
What developmental principle is illustrated by the activation of zygotic hunchback expression by Bicoid?
a gradient of a protein can activate a gene in a discrete region of an embryo through a threshold effect
Cell differentiation
all vertebrates make the same cell types where, when and in what quantity genes are expressed drives the difference between different species
Amniotes vs. Anamniotes
amniotic egg has yolk, amniotic sac, shell, chorion, allontois anamniotic egg just has yolk and jelly
When a Spemann organizer is grafted onto the ventral side of another gastrula, what happens?
an entirely twinned embryo with second d-v axis and head is created
What does DKK1 do?
antagonizes Wnt ventrally
What 3 maternal gene groups determine anterior-posterior axis?
anterior - bicoid posterior - nanos terminal - torso drosophila genes are named for what the mutant phenotype looks like if you move the protein to a different part of the egg, that structure will develop in the larvae i.e. move bicoid to the middle of the egg, then head structure will grow in the middle of the larvae
Where do eve stripes start?
anterior to posterior bias in development, more mature
What are the body axes?
anterior-posterior dorsal-ventral
asymmetric cell division
asymmetric distribution of cytoplasmic determinant, different daughter cells asymmetric self renewal - one differentiated daughter cell, one replicated daughter cell
How do you get a Spemann organizer?
below it is the Nieuwkoop center which signals for the Spemann organizer
Pattern Forming
bodies have polarity cells have their own polarity, apical, basal, etc. The major pattern forming process is known as gastrulation
Three main principles of DB
cell division, cell differentiation, morphogenesis
Name several mechanisms by which cells communicate with each other.
cell surface molecules on adjacent cells interact and initiate a signal transduction process that influences cellular behavior and gene expression cells form gap junctions with adjacent cells, allowing the passage of small molecules cells secrete proteins and small hydrophilic molecules, which interact with cell surface receptors on target cells and initiate a signal transduction process that influences cellular behavior and gene expression cells secrete small hydrophobic molecules which diffuse into target cells, interact with cytoplasmic receptors, and influence gene expression
Induction
cell-cell signaling direct contact diffusion gap junction
Briefly summarize the production of transgenic zebrafish.
check transgenic in the glossary (?) transgenic zebra fish are made by inserting DNA into a one cell embryo, as the embryo grows the DNA is incorporated with the original DNA of the zebra fish
What do bmp4 inhibitors do?
chordin, noggin turn on ventral genes and keep the other half of genes dorsal
Between fertilization and the first cleavage division, actin filaments pull the cytoplasm of the frog egg toward the point of sperm entry in a process called?
cortical rotation
So how do cells become different?
determination induction
What do maternal effect genes do?
determine the anterior-posterior axis
What is Waddington's Creode?
development is a marble in a sand pit individual cells as they progress through development faces different hills and valleys, and depending on what's in front of it and what cells are next to it, neighbors creating funnels
How do genes control development?
different genes are turned on or off for different areas and different stages of development, controlling where and when proteins are synthesized
What is the process by which developing cells achieve their functional, mature identity as liver, or muscle, or nerve cells called?
differentiation
Where is the inner cell mass located?
directly below the amnion/amniotic cavity
What do gap genes do?
divide embryo into broad segments and regulate pair rule genes
What genes control dorsal-ventral patterning?
dorsal Highest dorsal (mesoderm): twist snail (low affinity promoter) Intermediate dorsal: rhomboid (high affinity promoter) (neuroectoderm) single-minded (mesectoderm) little/no dorsal (high affinity promoter for dorsal, + corepressor): dpp, tolloid (dorsal ectoderm) zen (amnioserosa) notes: have to have enough dorsal but not too much dorsal-ventral regions as they're being patterned can either feed forward or feed back the dorsal most portion of the drosophila embryo has no dorsal in the nucleus if there's any dorsal detected, the dorsal most genes are not turned off dpp,zen = if there's no dorsal it won't be binding to the corepressors, turning on dorsal genes dorsal can be an activator or repressor —> study which one it is in each of these situations
Mutations in which genes or cascades would lead to a dorsalized embryo? How does this work? (Recall that genes in Drosophila are named for their mutant phenotype.)
dorsal mutant
What do dorsal and ventral vegetal cells do?
dorsal vegetal cells induce muscle and notochord from animal cap cells ventral vegetal cells induce blood and associated tissue from animal cap cells
Where is the Nieuwkoop center located?
dorsal vegetal side
What is tolloid?
dpp is secreted in the dorsal side secreted with toloid, tld when cells take on their ventral fate, Sog, when dpp and Tld get too far ventral, stops them Tld is the friend who promises the police, Sog, that they'll walk their friend to the right place Tld diffuses Sog BMP, Chorden, Noggin are human equivalents
What do the folding of sheets of cells, the migration of cells, and cell death all do for development?
drive morphogenesis
Where does the central nervous system come from?
ectoderm
What are the three cell layers?
ectoderm, endoderm, mesoderm
The central nervous system is derived from _____, the axial skeleton is derived from _____, and the muscles of the trunk are derived from _____?
ectoderm, mesoderm, mesoderm
2 central processes of DB
embryogenesis, morphogenesis
What are Hox genes? What do they encode?
encode transcription factors which specify a position along the anterior-posterior axis in vertebrates Hox genes are a family of genes that code for gene regulatory transcription factors
Where do organs come from?
endoderm
How do engrailed and eve interact?
engrailed is present at the beginning of each eve parasegment (and the end of each segment)
What do segment polarity genes do?
establish anterior-posterior gradient within each segment
What is the role of maternal factors (such as Vg-1, Xwnt-1, and VegT) in the vegetal region of the Xenopus oocyte?
establishing the future dorso-ventral body axis.
You are observing an embryo with gap genes and pair-rule genes. You notice elevated levels of giant and kruppel. How do you expect even-skipped will react?
every stripe is influenced in a different way by different proteins too much giant or kruppel won't turn off even-skipped
Where is bmp4 expressed?
everywhere in the embryo except Spemman's organizer
A transplant of eye region from neurula to host neurula vs gastrula to host neurula
eye region transplanted from gastrula to trunk of host neurula, graft cells develop in to trunk eye region transplanted from neurula to host neurula eye develops in the trunk
Briefly describe the pathway from a gene to a protein in eukaryotic cells.
first, transcription of RNA, then its processing, then its transport, then translation
How is the BMP4 gradient created?
from inhibitory factors from the organizer Chordin high on dorsal side (that's where it's made) Same with BMP on ventral side Use shuttling mechanism to spread gradient across cell
Morphogenesis and Gastrulation
gastrulation changes the shape of the embryo to a blastula, then undergoes gastrulation to make pattern forming, and then morphologically changes through morphogenesis to a gastrula other morphogenesis examples: apoptosis, cell differentiation
What happens in further dorsal refinement? (i.e. cell membranes have formed)
gastrulation rules (memorize those) - no one gene controls a process there's always at least two opposing forces cells cellularize — there are now cell membranes, individuals cells decapentaplegic (dpp) is secreted from these cells dpp, a morphagen, creates a morphogen gradient
housekeeping genes
genes that are switched on all the time because they are needed for life functions vital to an organism
Growth
growth is also on a cellular level myelination in the human brain doesn't end till 35 development continues to occur
What molecular cascades, first discovered through mutagenesis studies in Drosophila, also function in the development of mammals like us?
hedgehog homeobox genes the Wnt family the Toll signaling pathway
How do hedgehog, wingless and engrailed interact?
hedgehog and engrailed they co-occur at parasegment and segment boundaries wingless and hedgehog positive (?) feedback each other Wingless promotes engrailed
What is the drunken sailor model?
how do you refine the gradient? drunken sailor model morphogen gradient - a source and diffuse but there are things in the way, like "buildings" also, interacting with receptors, like "bars" if you get too "drunk" the "police" will stop you, aka enzymes that degrade the morphogen, "jail", or send it back to where it came from "sent back to ship"
How does Kruppel interact with bicoid and hunchback?
hunchback expression is completely anterior, cells are interpreting how much hunchback it sees tight band of expression (for all gap genes) too much hunchback or too little hunchback = turning Kruppel on (or any gap gene) Kruppel in a bicoid mutant - has a little bit of hunchback from mom but not at the level that would shut off kruppel
_____ is to bicoid as caudal is to ________
hunchback is to bicoid as caudal is to nanos
In chick development, what is the cell movement during gastrulation called?
ingression
How could we test that Wnt signaling drives organizer formation?
injecting B catenin into a ventral vegetal cell results in twinned embryo with duplicated axis
In mammalian development, the embryo will form from which population of cells?
inner cell mass
Briefly describe a generic cell signaling cascade starting from initiation and ending in cellular behavior.
interaction of a molecule with a receptor at the cell surface intracellular modification of proteins by phosphorylation production of second messengers such as cAMP
How do gap genes regulate each other?
interpretation of hunchback (master gap gene) gap genes create their own gradient, actively repress their neighbors cross repression creates tight patterns
What is the French Flag model?
it's all about positional information each cell has the potential to turn into blue red or white position of each cell is determined by the concentration of a morphogen positional value is interpreted by cells (thresholds) which differentiate to form a pattern 1 morphogen = french flag (or horizontal) 2 morphogens = english flag (or british to get more complicated) multiple morphagens with interactions = stars and stripes (or labyrinth)
What is engrailed?
key segmentation gene
In which portion of the frog's life-cycle would a frog appear most similar to a mammal?
late in organogenesis, at the phylotypic stage, the body plans of frogs and mammals are remarkably similar
What are maternal factors? What are they composed of?
mRNAs and proteins packaged into the egg by the mother, which act to control early development in the embryo
What creates the ectoderm in Xenopus?
maternal determinant gene called ectodermin
What makes the endoderm?
maternal determinant gene on vegetal pole makes endoderm
When do maternal and zygotic gene transcription and translation occur?
maternal gene transcription and translation begins before zygotic gene transcription and translation begin maternal genes (e.g. bicoid) zygotic genes: gap genes (e.g. hunchback, hb) pair-rule genes (e.g. eve, ftz) segmentation (e.g. wingless, wg) selector genes (abdominal A, abd-A)
Where do bones and the notochord come from?
mesoderm
The notochord is a ___ structure in vertebrate embryos that lies under the ___, and is flanked by ___.
mesodermal, neural tube, somites
Where is the blastopore?
on the dorsal side of the embryo
The ultimate goal of developmental biology is to understand human development. In your own words, discuss three areas of medicine that are impacted by the study of developmental biology.
oncology, immunology Can include clinical genetics, cancer, and regenerative medicine, etc.
This chapter discusses the embryonic development of Drosophila melanogaster. How long does embryonic development (before 1st instar larva hatches) take in this organism?
one day
The adult body plan of the fly is based on reiterating structures called segments. What genes direct segment precursors (parasegments) positioning at the cell-by-cell level?
pair-rule genes such as even-skipped
What is the establishment of the anterior-posterior or dorsal-ventral body axes called?
pattern formation
Determination
positive feedback - activator binds, gene 1 turns on gene 2, gene 2 turns on the activator negative feedback - activator turns on gene 3, gene 3 turns on gene 4, gene 4 turns off the activator development can be continual gene expression or can be short bursts
Remarkably, Vg-1 and wnt are used in both frogs and chicks to establish a body axis, although in chicks this is the antero-posterior axis instead of the dorso-ventral axis. What is the region of the chick embryo that is thus analogous to the Nieuwkoop center?
posterior marginal zone
Syncytial development
pre-cellularization sperm and egg fusion nuclear division = syncytium nuclei move to periphery of cytoplasm syncytial blastoderm and cellular blastoderm
During gastrulation in Xenopus, the future mesoderm and endoderm move inside the embryo through the "blastopore"; in contrast, in chickens, gastrulation involves cells moving inward through which structure?
primitive streak
What do pair rule genes do?
refine segment locations and regulate segment polarity genes
What body plan phenotype would result from a gap gene mutation? Why?
segments A2 through A6 would be missing, but the rest of the pattern is essentially normal
Signaling mechanism through phosphorylation
series of protein phosphorylation turns on/off transcription factor
Signaling mechanism through cell-cell contact
signal turns on co-activator, turns on/off transcription factor in the nucleus
Signaling mechanism through moving gene regulatory proteins
signal turns on/off signaling complex, releases transcription factor to the nucleus
What would be the effect of grafting an extra piece of notochord into a dorsal position adjacent to pre-somitic mesoderm?
signals from the notochord will convert presumptive dermomyotome into sclerotome (?)
two main types of cells
somatic cells (development) and germ line cells (migration and division) 1st gen: somatic cell 2nd gen: mutations in somatic cells do not affect germline germ line mutations 3rd gen: mutation in germ cell affects somatic cells and germ line
What is Weismann's model of development?
somatic development and change does not contribute directly to the characteristics of the next generation factors, or "determinants", in the nucleus regulate development asymmetric divisions result in unequal distribution of developmental determinants to daughter cells development is "mosaic"
What are germ cells?
sperm and oocytes
What kind of developmental defects are caused by mutations in homeotic genes?
the development of segments will be changed wholesale from their normal identity to that of a different segment
The grafting of the dorsal lip of the blastopore from an early Xenopus gastrula onto the ventral side of an early embryo results in what?
the formation of two sets of anterior structures joined along the ventral axis: a two-headed embryo
Describe, mechanistically, how the development of the antero-posterior axis of Drosophila is initiated.
the mother packages bicoid and nanos mRNA into the developing oocyte
The experiments of Spemann and Mangold first defined what feature of amphibian embryos?
the organizer
How are BMP and Chordin, and DPP and Sog related?
the same, just inverted by axis (in humans vs. drosophila)
What would be the effect on the timing of somite formation, if a piece of the pre-somitic mesoderm of a chick embryo is rotated by 180° and reinserted in its original position?
the timing of somite formation will be reversed in the rotated block only, proceeding from posterior to anterior, but the rest of the somites will form in a normal fashion, proceeding from anterior to posterior it will develop into the correct somite, but flipped 180 in position.
How does "torso" work?
torso-like trunk precursor processed trunk torso
The "mid-blastula transition" is the point in development when what happens?
transcription of zygotic genes begins.
What happens when a Nieuwkoop center of one cell is moved to the ventral side of a host cell?
twinned embryo develops with a duplicated axis
How to make dorsal mutant in terms of BMP and chordin?
under express BMP overexpress chordin make chordin difficult to bind to BMP
lateral inhibition
when one cell emits a certain type of activity, it inhibits the cells around it from also taking that identity
You go to monitor the hunchback levels in a bicoid mutant. What do you observe?
without bicoid, there can be no expression of hunchback hunchback expression depends on bicoid threshold and gap genes rely on hunchback thresholds
What is a fertilized egg called?
zygote
In frogs, maternally packaged Xwnt-11 leads to nuclear localization of _____ in the _____, which in response signals to adjacent cells to become the _____.
β-catenin, Nieuwkoop center, Spemann organizer
How is the Spemann organizer distinguished from the other mesodermal cells during induction by the cells of the vegetal region? In other words, how is it formed and what makes it different?
βcatenin, which has become localized to the nucleus in the Nieuwkoop center as a result of cortical rotation, turns on high levels of the TGF- signalling molecule, Nodal, and this relatively high level distinguishes the adjacent cells of the Spemann organizer from the rest of the mesoderm.