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AN4017 > L1 Stem Cell Niches & Developing Brain > Flashcards

L1 Stem Cell Niches & Developing Brain Flashcards

1
Q

Neural cell fates are determined in a __ manner

A

spatio-temporal

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2
Q

Neural stem cells are __potent

A

multi

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3
Q

Glial progenitors are __potent

A

bi (give rise to astrocytes & oligodendrocytes)

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4
Q

Neural progenitor cells can be either…

A

neurogenic or gliogenic

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5
Q

The neural plate is generated from __ by neural induction

A

dorsal ectoderm

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6
Q

__ antagonists induce generation of neuroectoderm

A

BMP antagonists (repress epidermal fate-inducing BMPs in overlying dorsal ectoderm)

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7
Q

Neural plate folds into __ , which detaches from epidermis

A

neural tube

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8
Q

Which occurs first: neurogenesis or gliogenesis?

A

Neurogenesis

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9
Q

The two types of division that NPCs of neural tube undergo

A

Symmetric division and asymmetric division

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10
Q

Symmetric division vs asymmetric division

A

Symmetric: two identical daughter cells (stem cells)
Asymmetric: one daughter cell continues dividing, one post-mitotic daughter cell delaminates from epithelium & differentiates into a neuron

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11
Q

What is the purpose of symmetric division?

A

to increase the number of NPCs to make the required number of neurons for optimal brain development

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12
Q

An example of an insult in early pregnancy that can affect neurogenesis

A

Zika virus can cause microcephaly

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13
Q

What are Delta and Notch?

A

Neurogenic genes that inhibit Neurogenin gene expression

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14
Q

What are Neurogenins?

A

a family of proneural genes that specify neuronal differentiation

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15
Q

What is an important gene for terminal neuronal differentiation?

A

NeuroD

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16
Q

What is the effect of Delta/Notch signalling?

A

It inhibits Neurogenin gene expression via TF inhibition

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17
Q

How do stem cells know to stay stem cells?

A

Lateral inhibition

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18
Q

What is lateral inhibition?

A
  • Discrete groups of neuroectodermal cells begin to express proneural genes & form proneural clusters
  • These cells then undergo an inhibitory cell-cell interaction, mediated via neurogenic genes, to determine which cells will differentiate into neurons
  • The first cell in proneural cluster begins to differentiate towards a neural fate, and sends out inhibitory signals to its neighbouring cell that inhibits it from becoming a neuron (remain precursor)
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19
Q

Most proneural genes encode…

A

basic helix-loop-helix (bHLH) transcription factors

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20
Q

Loss of proneural gene function leads to…

A

decreased neuronal production

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21
Q

Misexpression of proneural genes leads to…

A

increased neurons in neural tube & conversion of epidermal cells into neurons

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22
Q

Loss of neurogenic gene function causes…

A

a massive increase in neurons at the expense of other cells (epidermal cells in invertebrates; neural cells in vertebrates)

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23
Q

__ is recruited to apical pole to form the apical complex (Par/Insc/Pins), which directs…

A

Par complex
directs mitotic spindle orientation

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24
Q

During asymmetric cell division, the parent cell receives the __ complex

A

apical

25
Q

Proteins in the apical complex activate Delta/Notch signalling in neuroblasts, which leads to…

A
  • repression of proneural genes (and therefore, decreased neuronal production)
  • maintenance of stem cell state
26
Q

Apical complex causes movement of…

A

the basal complex (Ccnd2, Trim32) to basal pole

27
Q

During asymmetric cell division, the daughter cell receives the __ complex

A

basal

28
Q

What do basal complex transcription factors do?

A
  • Turn on genes for neural differentiation
  • Switch off genes for proliferation
  • Inhibit Notch signalling pathway (which de-represses proneural genes)
29
Q

RGC marker (asymmetric RGC divisions)

A

BLBP (brain lipid binding protein)

30
Q

Neural progenitor cell marker (symmetric cell divison)

A

Nestin (early neural tube)

31
Q

Does cell division happen at the apical or basal surface?

A

apical

32
Q

__ signalling keeps stem cells as stem cells

A

Delta/Notch

33
Q

Both daughter cells in symmetric division inherit the __ complex

A

apical

34
Q

Which daughter cell inherits the apical complex in asymmetric division?

A

the one closest to the apical surface

35
Q

In early development, NPCs are __ positive and __ negative

A

Nestin positive and BLBP negative

36
Q

What is neural patterning?

A

The biological process by which cells in the developing nervous system acquire distinct identities according to their specific spatial positions

37
Q

What is a major determinant of neuronal cell fate in the spinal cord?

A

dorsal-ventral positioning

38
Q

2 signalling centres at the ventral and dorsal midline

A
  • dorsal roof plate
  • ventral floor plate
39
Q

What does the dorsal roof plate secrete?

A

BMPs (bone morphogenetic proteins)

40
Q

What does the ventral floor plate secrete?

A

Sonic hedgehog (Shh)

41
Q

The absolute concentration of the __ acting on any one cell determines developmental fate

A

morphogen (e.g. BMP, Shh)

42
Q

Shh V-D gradient partitions the ventral floor plate into __ discrete progenitor domains, which generate __ different classes of neurons

A

5 domains, 6 neurons

43
Q

Does ventral patterning play a role in motor or sensory spinal circuitry?

A

motor

44
Q

Does dorsal patterning play a role in motor or sensory spinal circuitry?

A

sensory

45
Q

Motor neuron progenitors express…

A

Nkx6.1 and Olig2

46
Q

Neuron progenitors in other ventral domains become __

A

interneurons

47
Q

V3 interneuron progenitors express __ but not __ and __

A

express Nkx2.2 but not Pax6 & Olig2

48
Q

Nkx6.1 turns on expression of __

A

Olig2 (bHLH TF)

49
Q

Role of Olig2

A

induces motor neuron differentiation by activating expression of Hb9 and ISL-1/2

50
Q

The dorsal alar plate is subdivided into __ major progenitor regions. Describe

A

2
- most dorsal region (3 progenitor domains): Class A dI1-dI3 interneurons
- intermediate region (6 progenitor domains): Class B dI4-dI6 interneurons

51
Q

Wnt ligands bind to…

A

Frizzled receptors and co-receptors LRP5/6

52
Q

Mature BMP dimers exert their effects by binding to __, leading to…

A

BMPRs, leading to recruitment and phosphorylation of receptor-regulated Smad proteins (Smad-1/5), which then complex with Smad-4 and translocate to nucleus

53
Q

Neuron differentiation of Class __ interneurons is BMP/Wnt signalling-dependent

A

A

54
Q

The patterning of dorsal spinal cord interneurons requires __ signalling

A

BMP-Smad signalling

55
Q

BMP/Wnt signalling turns on expression of __, which are cell type specific determinants of Class A progenitors

A

Olig3, Atoh1 (dI1), Neurog-1/2 (dI2), Ascl1(dI3)

56
Q

__ is expressed by all Class A progenitors

A

Olig3

57
Q

Olig3 represses __ to specify dI1-dI3

A

Lbx1

58
Q

Neurogenesis has mainly been studied in the __, whereas neural patterning has mainly been studied in the __

A

cortex
spinal cord

AN4017 (8 decks)

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