neural dev

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  1. what are the 4 stages of neurulation?
    • 1. formation
    • 2. shaping of the neural plate
    • 3. furrowing, folding/bending
    • 4. fusion/closure
  2. What is the AVE?
    functions (4)?
    • Anterior viseral endoderm (Xenopus) = hypoblast (chick)
    • becomes extraembryonic tissue
    • inhibits multiple PS (Cerberus) & posterior neural, induces head structure, enforces anterior neural
  3. What is the origin of the neural tube?
    neural ectoderm -> neural plate -> neural tube -> C/P-NS (brain & spinal cord)
  4. what is convergent extension?
    when is it important?
    how is it controlled?
    • lateral cells move toward the midline/medially -> A/P axis extension during neural plate folding
    • by Wnt -- Frz --> Dsh ->  cytoskeletal regulators (Rho/CDC242) -> lateral cell movement toward midline
  5. What is planar cell polarity?
    why is it important?
    • PCP directs epithelial cell migration between directional migration or asymmetric deposition of cellular extensions (*convergent extension)
    • establishes cytoskeletal asymmetry & positioning of basal bodies (due to differential localization of PCP signalling components)
  6. what is apical constriction?
    what does it involve & why is it important?
    apical constriction of the actin/myosin cytoskeleton in neural plate epithelial cells promotes neural folding by creating tension along the neural plate via non-muscle myosin II
  7. How can you track transcription factor expression?
    • in situ hybridization 
    • antibody staining
  8. what is the mid-gastrula organizer?
    • mid-gastrula organizer -> Chordin -// BMP -> anterior neural
    • GO becomes node
  9. AVE KO?
    GO/Node KO?
    • AVE KO = no head, yet normal posterior neural
    • node KO = no posterior, yet some anterior
    • therefore AVE necessary for head & inhibits posterior & induces some anterior
    • node necessary for posterior & some anterior
  10. how does the neural tube fold & close? (5 steps)
    • formation of neural plate = Δcell shape -> taller along apical-basal axis
    • shaping of NP = Δcell shape via convergent extension - L->M & A/P ext
    • furrowing = apical constriction (myo-actin cytoskeletal tension) & hinges
    • folding = surface & neural ecto cell-cell adhesion  & surface ecto pulling toward dorsal midline
    • closure = lateral edges of neural tube fuse (E-cadherins) at fusion points
  11. What secreted molecules are necessary for splitting of the eye field?
    where are they secreted from?
    • Sonic hedgehog (Shh)
    • BMP
    • from (anterior) prechordal plate/endomesoderm
  12. Shh signalling =?
    • Shh signalling = morphogen for TF -> ventral neuron patterning (notochord & floorplate)
    • in primary CILIA
    • Shh -> Patched (Rec) -> internalized Patched thus disinhibited Smoothened Rec to membrane
    • Smoothened -> prevents Ci/Gli phosphorylation & degradation -> transcription -> (*Pax1 -> ventral somite patterning) patterning of the neural tube & limp development
  13. Dorsal neural patterning molecules?
    Wnts & BMPs (roofplate)
  14. what are integrin receptors important for?
    binds (4)?
    • integrin receptors mediate cell adhesion & migration thru the blastopore providing an indirect link between the cell's actin skeleton & the ECM
    • binds ECM ligands (Fibronectin, Vitronectin, Laminin, Collagen)
  15. focal adhesions?
    focal adhesions are the link between F-actin of the cytoskeleton & the ECM cytoplasmic component to create anchor necessary for cell movement
  16. What is the result of UV irradiation? why?
    ventralized embryo due to prevention of cortical rotation & the formation of the organizer
  17. Neural induction?
    pharyngeal endomesoderm, prechordal plate & dorsal mesoderm (notochord) migrate under ectoderm & Noggin & Chordin -// BMP -> neural tissue (trunk & spinal cord)
  18. head induction?
    signals from the prechordal plate Cerberus, FzzB & Dkk (from the AVE) inhibit Wnts & BMP -> head structures
  19. (3) sources of positional info in neurulation?
    where & interactions?
    • the gradient of RA, FGF & Wnt along A/P axis pattern the neural ectoderm
    • RA gradient A-P -//FGF (P-A) - NO RA in head or tail regions (CYP26)
    • Wnt expressed dorsally in the ectoderm from roofplate
  20. epidermal signals
    BMP & Wnts
  21. anterior birth defects in neural tube folding?
    • facial cleft
    • spina bifida - open posteriorly
    • exencephaly - exposed brain
    • open neural tube
  22. PCP KO?
    lack of directional info (L-M, D-P, A-B...) = defect in neural tube closure due to loss of convergent extension = open neural tube (trunk)
  23. non-canonical Wnt signalling is important for?
    • cell migration
    • Wnt -> Frzl -> Dsh -> cytoskeleton -> cellular movement
  24. Neural crest cells =?
    • thru anterior half of somites = PNS neurons (dorsal root ganglia)
    • btwn surface ectoderm & dermamyotome = pigment cells 
    • dorsal to the neural tube & lateral to the neural fold
  25. NCC EMT signalling?
    ectodermal BMP -> mesenchymal transition thru RhoB & Slug -// cadherins
  26. Notch vs. Numb?
    • asymmetrical cell division:
    • Notch only cells = neuroblast (basal)
    • Numb only = stem cells (apical)
    • symmetrical cell division:
    • Notch & Numb = 2 stem cells
  27. what controls D-V patterning of the spinal column?
    Lim family transcription factors that are differentially expressed -> diff identity & function of motor neurons
  28. what controls A-P patterning of the spinal column?
    Hox genes therefore A/5'end/#1 Hox genes = cervical & P/3'end/#13 = caudal...
  29. what controls axon guidance?
    At the distal tip of the axon is the growth cone that expresses diff. receptors that are sensitive to attractive & repulsive short & long range signals guiding axon migration
  30. long range signals of axon guidance?
    • secreted factors
    • (in Drosophila) DCC+Netrin = attractive
    • Robo + Slit = repulsive
  31. Netrin is required for?
    in vertebrates (conserved) the DCC homologous receptor must bind Netrin to guide Commissural axons to connect the dorsal part of the neural tube to the floorplate
  32. (3) types of neurons?
    • Commissural = connections in brain & spinal cord
    • interneurons = connects motor neurons to dorsal root ganglia
    • motor neurons = connects spinal cord to muscle to allow movement
  33. Neurogenin
    • transcription factor interacting with:
    • Δ = increased neurogenin & Δ expression -> neuroblast & eventual inhibition of neighboring cell from expressing neurogenin 
    • NeuroD = TF -> neuron specification genes -> neurons
  34. short range signals of axon guidance?
    • transmembrane receptors thus req. cell-cell contact so:
    • Cadherins = attractive
    • Ephrins = repulsive
  35. Ephrine?
    • short range repulsive signal expressed in posterior half of somites
    • binds to neighboring (NCC) cells Eph receptor guiding axon through anterior of the somites
  36. Example of how to map NCC movement?
    • Quail neural tube cells transplanted into chick embryo (same place & dev stage) & track with Quail antibodies
    • Use a fluorescently tagged NCC cells
Card Set
neural dev
neural development & induction
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