L1 Stem Cell Niches & Developing Brain

Question 1

Neural cell fates are determined in a __ manner

Answer 1

spatio-temporal

Question 2

Neural stem cells are __potent

Answer 2

multi

Question 3

Glial progenitors are __potent

Answer 3

bi (give rise to astrocytes & oligodendrocytes)

Question 4

Neural progenitor cells can be either…

Answer 4

neurogenic or gliogenic

Question 5

The neural plate is generated from __ by neural induction

Answer 5

dorsal ectoderm

Question 6

__ antagonists induce generation of neuroectoderm

Answer 6

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

Question 7

Neural plate folds into __ , which detaches from epidermis

Answer 7

neural tube

Question 8

Which occurs first: neurogenesis or gliogenesis?

Answer 8

Neurogenesis

Question 9

The two types of division that NPCs of neural tube undergo

Answer 9

Symmetric division and asymmetric division

Question 10

Symmetric division vs asymmetric division

Answer 10

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

Question 11

What is the purpose of symmetric division?

Answer 11

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

Question 12

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

Answer 12

Zika virus can cause microcephaly

Question 13

What are Delta and Notch?

Answer 13

Neurogenic genes that inhibit Neurogenin gene expression

Question 14

What are Neurogenins?

Answer 14

a family of proneural genes that specify neuronal differentiation

Question 15

What is an important gene for terminal neuronal differentiation?

Answer 15

NeuroD

Question 16

What is the effect of Delta/Notch signalling?

Answer 16

It inhibits Neurogenin gene expression via TF inhibition

Question 17

How do stem cells know to stay stem cells?

Answer 17

Lateral inhibition

Question 18

What is lateral inhibition?

Answer 18

• 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)

Question 19

Most proneural genes encode…

Answer 19

basic helix-loop-helix (bHLH) transcription factors

Question 20

Loss of proneural gene function leads to…

Answer 20

decreased neuronal production

Question 21

Misexpression of proneural genes leads to…

Answer 21

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

Question 22

Loss of neurogenic gene function causes…

Answer 22

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

Question 23

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

Answer 23

Par complex
directs mitotic spindle orientation

Question 24

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

Answer 24

apical

Question 25

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

Answer 25

- repression of proneural genes (and therefore, decreased neuronal production) - maintenance of stem cell state

Question 26

Apical complex causes movement of...

Answer 26

the basal complex (Ccnd2, Trim32) to basal pole

Question 27

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

Answer 27

basal

Question 28

What do basal complex transcription factors do?

Answer 28

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

Question 29

RGC marker (asymmetric RGC divisions)

Answer 29

BLBP (brain lipid binding protein)

Question 30

Neural progenitor cell marker (symmetric cell divison)

Answer 30

Nestin (early neural tube)

Question 31

Does cell division happen at the apical or basal surface?

Answer 31

apical

Question 32

__ signalling keeps stem cells as stem cells

Answer 32

Delta/Notch

Question 33

Both daughter cells in symmetric division inherit the __ complex

Answer 33

apical

Question 34

Which daughter cell inherits the apical complex in asymmetric division?

Answer 34

the one closest to the apical surface

Question 35

In early development, NPCs are __ positive and __ negative

Answer 35

Nestin positive and BLBP negative

Question 36

What is neural patterning?

Answer 36

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

Question 37

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

Answer 37

dorsal-ventral positioning

Question 38

2 signalling centres at the ventral and dorsal midline

Answer 38

- dorsal roof plate - ventral floor plate

Question 39

What does the dorsal roof plate secrete?

Answer 39

BMPs (bone morphogenetic proteins)

Question 40

What does the ventral floor plate secrete?

Answer 40

Sonic hedgehog (Shh)

Question 41

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

Answer 41

morphogen (e.g. BMP, Shh)

Question 42

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

Answer 42

5 domains, 6 neurons

Question 43

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

Answer 43

motor

Question 44

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

Answer 44

sensory

Question 45

Motor neuron progenitors express...

Answer 45

Nkx6.1 and Olig2

Question 46

Neuron progenitors in other ventral domains become __

Answer 46

interneurons

Question 47

V3 interneuron progenitors express __ but not __ and __

Answer 47

express Nkx2.2 but not Pax6 & Olig2

Question 48

Nkx6.1 turns on expression of __

Answer 48

Olig2 (bHLH TF)

Question 49

Role of Olig2

Answer 49

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

Question 50

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

Answer 50

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

Question 51

Wnt ligands bind to...

Answer 51

Frizzled receptors and co-receptors LRP5/6

Question 52

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

Answer 52

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

Question 53

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

Answer 53

A

Question 54

The patterning of dorsal spinal cord interneurons requires __ signalling

Answer 54

BMP-Smad signalling

Question 55

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

Answer 55

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

Question 56

__ is expressed by all Class A progenitors

Answer 56

Olig3

Question 57

Olig3 represses __ to specify dI1-dI3

Answer 57

Lbx1

Question 58

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

Answer 58

cortex spinal cord