Term
Describe the results of Wilhem Roux's experiments and how they led to the development of Mosaic Theory.
How was this theory influenced by the Discover of Dreish and Spemann? |
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Definition
He took embryos and damaged half of the cells. He found that you end up with half of an organism, and hypothesized that cell fate must therefore be completely pre-determined.
When Dreish and Spemann split embryos and found that each half developed into a complete organism, they discovered pluripotency. |
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Term
| By what 3 mechanisms can Enhancers/Repressors alter DNA transcription? |
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Definition
1) Second messengers: cAMP-CREB
2) Steroid receptors: migrate to nucleus and act as t factor
3) Tissue specific: certain molecular signals expressed only in certain areas |
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Term
| What is the molecular mechanism through which BMP inhibits neurulation in the developing embryo? |
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Definition
- BMP is a TGF-beta family member that binds a ligand at receptor 1
- Receptor 1 activation leads to activation of receptor 2 (kinase), which phosphorylates 1, and leads to phosphorylation of R-smads
- Rsmads form complexes with co-smads and migrate to nucleus where they act as transcription factors. |
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Term
| How does Wnt signaling influence neural induction? |
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Definition
1) Wnt acts as a transformer (posteriorizing factor)
- Co-inhibition using Dk11 and noggin (BMP) leads to induction of anterior neural structures
2) Mechanism
- Wnt binds Frzled receptor, causing Discheveled to block degradation of Beta-catenin complex (it then travels to nucleus and acts as t factor) |
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Term
| What are Blastospores and how do they arise? |
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Definition
- Location where blastosphere invaginates during gastrulation and cells destined to become endoderm and mesoderm enter.
- When egg is penetrated by sperm, it undergoes cleavages that result in the formation of blastomeres, which form spheres called blastospheres. |
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Term
| How did Spemann's experiments influence how we think about neural induction? |
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Definition
- Found that mesoderm, led by dorsal lip of blastopore, is responsible for inducing overlying ectoderm to become neural tissue. This lip, or "organizer," is the only self-differentiating region of the early gastrula
- He destroyed this tissue and found that neural ectoderm was not induced
- He then transplanted dorsal lip tissue into a secondary site and found that it produced an additional body axis. |
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Term
| What are the major neural inducers that are released by the organizer region of the mesoderm and how do they function? |
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Definition
| Noggin, Chordin and Follastatin inhibit BMP signaling via inhibition of activin receptor signalling, thereby providing a permissive signal for neurogenesis. |
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Term
| What is the evidence for the idea that the default state of ectodermal development is neural? |
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Definition
IF you dissociate the animal cap tissue of the embryo , then you get neurons where you would otherwise get epidermis.
This defualt state is blocked by BMP signaling, and then enabled through BMP inhibition by Noggin/Chordin/Follastatin |
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Term
| How are ectodermal cells determined to become neurons vs. skin cells? |
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Definition
Lateral Inhibition via Notch-delta signalling.
- Neuroblasts that express ASC inhibit adjacent proneural cells in ectoderm via Notch (transmembrane protein) signaling, which when bound by Delta, leads to transcription of repressive HLH t factors that prevent further Delta production.
- "If you get hit by neighbors delta, you cannot make enough delta to inhibit your neighbor" |
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Term
| Describe the steps of Neurulation. |
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Definition
- Neural plate forms after gastrulation
- Neural crest plates fuse as neural tube forms from plate (R to caudal direction)
- Actin and N-Cadherin are essential for adherence of NC plates during tube formation
- Folic acid is important for neural tube closure (overcomes deficit in methionine synthase that can lead to spina bifid a) |
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Term
| What are bicoid and nannos and how do they relate to the development of cell polarity? |
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Definition
| Bicoid (anterior t factor) and Nannos (posterior rna binding protein) determine A-P polarity is drosophila oocytes by determining Gap gene expression during segmentation. |
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Term
| What are hox genes and how to they contribute to embryonic patterning? |
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Definition
Transcription factors that are expressed topographically along the chromosome during segment determination (5' is anterior and 3' is posterior) and are important for Rostro-Caudal identity, most notably in the rhomobmeres of the hindbrain, where they lead to creation of cranial nerve nuclei.
Experimentally, there expression precedes anatomical division. |
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Term
| How does RA contribute to embryonic patterning? |
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Definition
- Determines AP patterning by regulating hox gene expression in the hindbrain (posteriorizing molecule).
- Diffuses from mesoderm to hindbrain and binds cytosplasmic factors that travel to nucleus and act on RAREs |
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Term
| How does RA contribute to embryonic patterning? |
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Definition
- Determines AP patterning by regulating hox gene expression in the hindbrain (posteriorizing molecule).
- Diffuses from mesoderm to hindbrain and binds cytosplasmic factors that travel to nucleus and act on RAREs |
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Term
| How does Shh signaling contribute to embryonic patterning? |
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Definition
DV patterning and sensory (roof)/motor (floor) determination.
- Secreted glycoprotein that induces ventral development of motorneurons (explants of Shh leads to motor neuron induction)
- Gradient determines motor neuron type.
**Dorsal plate develops in absence of Shh, but also requires BMP, Wnt and RA signalling for proper development** |
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Term
| Describe Nieukwoop's activator/transformer theory. |
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Definition
- Activators are released by organizer (dorsal lip of blastopore) to cause ectodermal cells to develop anterior characteristics (examples include Noggin and Chordin).
- Transformers are required to transform neural tissue into hindbrain and spinal chord (RA, Wnt, FGF) |
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Term
| What are the basic organizing centers that arise form the neural tube? |
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Definition
1) Prosencephalon, Mesencephalon, Rhombencephalon
2) Become TDMMM |
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Term
| Describe Le Douarin's experiments with Chicks and Quails and how they contributed to our understanding of fate mapping in the developing nervous system? |
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Definition
- Transplant mesencephalon (midbrain) and found that it induces formation of metencephalon (cerebellum)
- Mes-Met boundary has Wnt, engrailed and FgF8, which are required for proper midbrain/cerebellum formation
- FGF8 is expressed in cells that also express Otx2 and Gbx2 |
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Term
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Definition
| Transcription factors with homeobox domains that define regional differences in anterior brain (Pax6 in retinal development) |
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Term
| What are CAMs and how do they contribute to axonal pathfinding? |
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Definition
CAMs are part of the IgG superfamily of calcium-dependent cadherins.
- They bind homophillically between axons via non-sialated residues. A finder axon expresses CAMs that followers are attracted to.
- A variable extracellular portion is variably sialylated to regulate adherence, and an intracellular portion interacts with cytoskeletal elements.
- Axons de-fasciculate by expressing more sialic acid, and then find their targets by following molecular cues.
- Regulation: Fasciclin II is adhesive and Beat-1a is anti-adhesive |
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Term
| How does CNTF determine glial fate? |
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Definition
A mitogen that causes fate restriction in partially-restricted progenitors.
CNTF binds receptor and leads to STAT phosphorylation, which acts as a glial-specific t factor. |
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Term
| Where are neural progenitor cells found in the neural tube and how do they develop? |
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Definition
Cortical columns come from single progenitor! (3H-thymidine labeling and Retroviral lineage tracing)
- Ventricular zone lining of central canal
- Their cell cycles get longer during embryogenesis, as they transition from the expansion to neurogenesis stages.
- Number of fate possibilities decreases during embryogenesis, as gene expression becomes increasingly restricted and less sensitive to enviornment. |
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Term
| What are the major stages of neurogenesis? |
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Definition
Expansion: Low Q faction
- initially symmetric (2 progenitors), but becomes asymmetric (1 neuron and 1 progenitor)
Neurogenic: High Q fraction |
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Term
| What are the determinants of the number of neurons a progenitor cell can make? |
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Definition
1) IPCs control total number
2) Mitogens (FGF, EGF)
3) Cell-cycle genes (cyclin, CDKs, Rb, P53, ect)
4) Notch-delta signaling (Hes gene activation, which maintains pluripotency by inhibiting tumor suppressor genes). |
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Term
| How does the action of CDKs regulate the cell cycle? |
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Definition
| Phosphorylate Rb, which releases E2F1 t factor that leads to G1-S transition. |
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Term
| How is Microcephaly a disease of Neurogenesis? |
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Definition
| ASPM gene mutation disrupts symmetric division during the expansion phase and causes neurogenic division to occur too early. |
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Term
| Describe how mechanosensory neuron fate is determined in C. elegans and why it is an example of a "transcriptional hierarchy." |
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Definition
- Q cells divide into Q1.a and Q1.p.
- Q1.p has unc-86 (t factor), which increases mec-3 expression. This is necessary for differentiation of interneurons into touch neuron's
**Unc-86 is also involved in NT expression in egg-laying neurons** |
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Term
| What developmental principle is illustrated by the chemical sensitivity of ASE gustatory neurons? |
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Definition
| They are morphological mirror images, yet they are sensitive to different chemicals depending on the SPATIOTEMPORAL expression of transcription factors (hierarchy). |
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Term
| What is the defect in Lissencephaly? |
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Definition
| Nueral migration issue leading to smooth brain. |
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Term
| What are the major progenitor cell types in cortical development? |
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Definition
1) Radial glial progenitors are found in the body of the VZ and extend to the pia
- newly born neurons climb radial glial processes to form neural pre-plate (CR cells).
- newly post-mitotic pre-plate cells then become cortical plate
- Development is inside-out.
2) IPCs grow radially and become neurons and other IPCs or glia (amplification)
- control thickness of various cortical layers |
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Term
| What is the "radial unit hypothesis"? |
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Definition
| Evolution favors increased radial units to expand the cortex (relative cell numbers in each column are determined by IPCs). |
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Term
| How are GABA interneurons of the MGE different in their migration patterns from normal neural precursors? |
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Definition
| They migrate tangentially. |
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Term
| What have we learned from reeler gene mutations? |
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Definition
Secreted glycoprotein expressed by CR neurons
- Mutations cause ataxia and tremor, and lead to "outside-in" cortical development
- Reeler binds APoER1 receptors on migrating neurons, leading to DAb1 association with ApoER1 cytoplasmic cells.
- Dab1 is phosphorylates by SRC kinase and leads to cytoskeletal rearrangements.
- Dab1 is targeted by proteosomal degredation by Cul-5, which when suppressed, leads them to overgrow their target (stop signal is Dab degredation). |
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Term
| What are Neural crest cells and what do they give rise to? |
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Definition
1) Arise from epithelial cells of neural plate border in neural tube (express Snail/Sox/Fox/Sox)
2) Give rise to cranial bones, melanocytes, schwann cells, enteric nerve plexus, parasympathetics, AP septum, ect. |
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Term
| How does Neural crest induction occur? |
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Definition
1) BMP/BMP antagonist gradients set up neural borders in neural tube
2) Wnt/FGF/RA signaling creates NC potential by maintaining multipoint precursors.
3) Notch/Delta signaling subdivides lineages of NC progenitors and BMP/Slug signalling leads to their emigration. |
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Term
| What factors determine the migration path of NC cells? |
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Definition
Molecules, location and timing.
1) R-C axis location
2) Timing
3) Molecular cues (Wnt for sensory and pigment and Nrg-1 for schwann). |
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Term
| How is the fate of NC cells determined? |
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Definition
Both intrinsic and environment!
1) Vagal NC populations will develop into sympathetic structures when placed in trunk locations (environment)
2) Duck neurons maintain their morphology when transplanted into qual (intrinsic) |
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Term
| What is Treacher-Collins syndrome? |
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Definition
| Neurocristopathy where TCOF-1 mutation (AD) disrupts ribosome biosynthesis in NC cells, altering eyes, cheek bones, ears and jaws due to increased tumor suppressor expressio in neuroepithelial cells and increased apoptosis. |
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Term
| What population of cells is affected in Hirschsprung's disease? |
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Definition
| Aganglionic megacolon due to defect in survival/pathfinding/proliferation of sacral neural crest cell populations |
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Term
| Describe the major events that lead up to gastrulation. |
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Definition
1) ICM becomes epiblast (ecto)/hypoblast (endo)
2) At gastrulation, epithelial cells transition to mesenchymal cells that dive through cell layers to form the primitive street (A-P direction)
3) Ecto (skin and neural tube), Meso (muscle, cartilage, bone), and Endo (gut lining and resp epithelium). |
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