L13

Question 1

Fate choice of NSCs…
(BP= basal progenitor)
BP->proneural function->result

Answer 1

BP->gliogenic gene expression inhibited-> gliogenesis inhibited
BP->Sox2 expression inhibited-> exit stem cell mode
BP->Sox21 activated->inhibits Sox 2 activity-> exit stem cell mode
BP->Cdk inhibitors activated to arrest cell cycle-> differentiate
BP-> maintain proneural gene expression->activates gliogenesis
BP-> Delta-Notch to undetermined radial glia neighbour (peak NGN never coincided with cell division so never switched to BP-> HES threshold reached)->glial progenitor

Question 2

[in mouse cerebral cortex]

Answer 2

Wt- E11 cells + LIF cytokine -> Ns after 1/2 divisions, astrocytes after 5; Culture E15 cells-> astrocytes
Mice w/o JAK-STAT signalling components- E15 show impaired astrocytes differentiation -> JAK-STAT is important for switching from N to G(astro)

Question 3

What does over expression of JAK-STAT cause?

Answer 3

Early switch to astrocyte formation, which means less neurons (JAK-STAT in C21… Down’s)

Question 4

Proneural genes…

Answer 4

…drive neurogenesis, during which lateral inhibition keeps many NSCs suppressed-> basal progenitors generate Ns that differentiate and signal to NSCs so suppressed NSCs can now tale gliogenic path

Question 5

JAK-STAT regulation

Answer 5

LIF binds LIFRβ:gp130(cardiotropin in vert) -> JAK1 dephosphorylated -> phosphoryl groups bind to STAT1/3 (x2) -> dimerise -> activate JAK-STAT genes -> neurogenesis inhibited, gliogenesis auto-upregulated

Question 6

Fate determination in neural crest cells…

Answer 6

…trunk neural crest cells regions s7-s22; NGN+ve neural crest cells form sensory neurons and Schwann cells of PNS

Question 7

What is Nrg-1?

Answer 7

Glial inducing factor in neural crest cells (50:50 glia to neuron without, 100:0 with)

Question 8

Retinal column

Answer 8

RGC->horizontal cell->amacrine cell->cone->bipolar cell->rod->Müller cell
Each cell has distinct fate due to change in bHLH and Hox identity code after each division

Question 9

Optic nerve

Answer 9

O2A progenitors derive from ventral diencephalon (Pax2, Sc3) -> migrate into optic nerve and differentiate into neurons/ oligodendrocytes due to extrinsic signals; RGC axons passing from retina through optic nerve secrete PGDF-> promote oligodendrocyte which wrap RGC (thus O2A progenitors do not generate neurons but still need neuronal cues

Question 10

Table of identity codes

Answer 10

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