Neural Induction Flashcards
When does neural induction occur
Gastrulation
Gastrulation
Process of forming germ layers, the most important event in neural development!
Blastomere
Cells from early mitotic divisions that form the blastula
Blastula
Sphere of cells made of blastomeres
Blastocoel
Fluid filled cavity where cells move around
C. elegans
A worm in which we can map out all 350 cells
First division of C. elegans
AB blastomere and P1 blastomere
AB blastomere of C. elegans
Forms hypodermal tissue
How does the AB blastomere develop
Offspring of AB blastomeres begin to form an external surface around the other blastomeres
Which blastomeres form the interior of the C. elegans embryo
MS, E, C, and D
Where are neurons in C. elegans derived from
The ventrolateral surface through division of AB outer layer
Where is the nervous system formed in invertebrates
Ventrolateral side
Explain how the germ layers in drosophila separate.
- The mesoderm involutes inside the embryo on the ventral side, then separates to go completely inside the embryo.
- The neurogenic regions that were previously on the side join together on the ventral side of the embryo.
Explain the process of delamination in Drosophila
Neuroblasts on the ventral side of the embryo separate from the ectoderm by swelling and popping out of the epithelium
How are more neuron cells made
Ganglion mother cells divide to form neuronal cells while neuroblasts divide to create more GMC
Ganglion mother cell
First cell division of a neuroblast
Animal pole of the blastula
The dorsal part of the blastula, becomes ectoderm
Vegetal pole of the blastula
Ventral part of the blastula, becomes endoderm
Involuting marginal zone
Portion of the embryo that slides inside the embryo into the blastopore
Blastopore
Hole that forms on the opposite side of sperm entry
Why do embryos have poles?
Polarization of the embryos help facilitate division
What happens to frog blastomeres during the 2nd division
Animal blastomeres are much smaller than the vegetal blastomeres
How is mesoderm formed in frog cells?
Cells in the IMZ (which are dorsal to blastopore) comes inside the blastopore to then become mesoderm
Where does neural tissue in frogs come from?
The ectoderm that lies above the mesoderm becomes the neurogenic region.
Dorsal blastopore lip
The dorsal edge of the blastopore
Neural plate
The ectoderm above the mesoderm, forms the central nervous system
What effect does yolk have on human embryos?
Human eggs have very little yolk, which results in more uniform divisions
Blastocyst in human embryos
Forms after multiple cleavage divisions
Inner cell mass and outer cells of blastocyst
Inner cell mass of the blastocyst becomes the embryo, while the outer cells become the placenta
The embryo becomes _________ at the point of __________
The embryo becomes elongated at the point of gastrulation
Primitive pit
Human version of a blastopore
Primitive streak
Forms from the primitive pit
How does the neural tube form from the neural plate?
- The neural plate folds and comes together at the neural crests.
- The part of the neural plate that has formed a loop becomes the neural tube, while the neural plate above the tube becomes epidermis.
What is the experimental evidence that neural cells are induced during gastrulation?
An pre-gastrulation isolated animal cap turns into epidermis, while an animal cap isolated after gastrulation becomes neural tissue
Spemann organizer
- Extracted DBL (which is already essentially mesoderm) and implanted it into another developing frog
- Ended up with 2 nervous systems, which suggests mesoderm induces neural development
What is formed from an isolated animal cap?
Nothing, no mesoderm develops and therefore no neural tissue
What forms when mesoderm is removed from animal and vegetal caps?
A new mesoderm forms
Hyperdorsalized tadpole
Nervous system is dorsal, so a tadpole with too much nervous system
What happens when a frog egg is treated with UV?
Results in a ventralized embryo
What happens when a frog egg is treated with Lithium?
Hyperdorsalized embryo
What happens when a UV-treated animal cap and Lithium soup are combined?
Relatively normal embryo
Noggin
A molecule that induces nervous system development by telling ectoderm that it will become neural tissue
BMP
BMP inhibits neural induction, prevent cells from defaulting to neural fate
How does noggin lead to a neural fate?
Noggin is an antagonist of BMP, which binds to TGF-beta receptors. Noggin blocks BMP from binding, which prevents an epidermal fate from happening. This leads to the default neural fate turning on.
What are the 3 candidate molecules for neural induction?
Noggin, chordin, and follistatin
Follistatin
- Released from the pituitary gland
- Inhibits activin as a part of the TGF-beta molecule family
- The first molecule for understanding the puzzle
How does follistatin work?
An antagonist of the activin receptor
Lateral inhibition
Cells that touch each other inhibit each other form becoming neural through binding of BMP
Experimental results of lateral inhibition
An isolated animal cap that stays intact becomes epidermis, while a dissociated animal cap becomes neurons. A dissociated animal cap with BMP added becomes epidermal cells.
Which BMPs do BMP inhibitors bind to?
Noggin and chordin bind to BMP4, while follistatin binds to BMP7.
Where do noggin, follistatin, and chordin come from?
Secreted by the mesoderm onto the neural plate
Where is BMP made
Actively made in the ectoderm
Explain BMP signaling pathway for epidermal fate.
BMP binding to TGF-beta receptors leads to Smad binding to Zic 1 gene. This represses the Zic1 gene, which cuts off the pipeline for pro neural gene expression
Explain the BMP signaling pathway for pro-neural fate
Noggin, chordin, and follistatin prevent BMP from working on Smad, and therefore Zic1. Zic1 is no longer repressed which results in neural fate
FGF and Zic3 in proneural pathways
Fibroblast growth factors (FGF) bind to FGF-R which leads to ERK signaling factor activating Zic3. Zic3 helps further emphasize a pro-neural fate
Do we need Zic3?
Zic3 is only mandatory in chickens, but all vertebrates want to have both Zic1 and Zic3 expressed. Allows for a backup plan
What happens to neural and head development without neural inducers?
Knocking out one neural inducer leads to a relatively normal mammal, but knocking out two leads to significant deficiencies.
Short gastrulation (sog)
Gene in drosophila that is homologous to chordin made in the ectoderm
Decapentaplegic (DPP)
Drosophila version of BMP
What happens in mutant organisms with no sog?
There is a smaller or nonexistent neurogenic region.
What happens in mutant organisms with no DPP?
No inhibition of neural growth, which leads to too much nervous tissue/larger neurogenic region
How does the timeline for neural induction compare in drosophila vs. frogs? [INCOMPLETE]
IDK, FIX THIS
Lateral inhibition in drosophila
Killing a delaminating neuroblast causes one of the adjacent ectoderm cells to take its place as the new neuroblast
Achaete-Scute (A-Sc)
- Collection of 4 pro-neural genes
- Basic helix-loop-helix transcription factors to turn on neural fate genes
Explain tribute picking of neuroblast hunger games
Before neuroblasts delaminate, all areas that we could possibly want to be neuroblasts have sog active. We then pick a cluster of tributes (potential neuroblasts) and begin the battle
Why have the neuroblast hunger games in the first place?
Allows for a backup system if any neuroblasts get damaged in the neural formation
A-Sc levels in neuroblasts at beginning of hunger games
Made at low levels in the neuroblast tribute cluster
What happens to A-Sc levels once a winner of the neuroblast hunger games is decided
The winning tribute amplifies A-Sc expression in itself and silences expression of it in the other tributes, which results in one cell with higher level of A-Sc
Pathway of A-Sc, Delta, and Notch
- A-Sc activity leads to production of Delta which binds to the Notch receptors of neuroblast losers
- Notch interacts with Mastermind (MAM) in the nucleus
- Complex of MAM and Notch recruit SuH which gets rid of co-repressor on E(spl) gene
- Transcription of E(spl) gene represses A-Sc in loser neuroblasts?
