Neuronal Stem Cells (NSC) in the Central Nervous System (CNS)

Question 1

Define self renew

Answer 1

Capacity to proliferate to produce multiple cells

Question 2

Define multipotent

Answer 2

capacity to differentiate to produce major cell lineages (e.g. neurons, astrocytes)

Question 3

Neural plate forms at __ weeks gestation

Answer 3

Neural plate forms at 3 weeks gestation

Question 4

Where do PNS cells arise from?

Answer 4

Neural Crest

Question 5

3 Brain vesicles formed from the closure of the rostral neuropore?

Answer 5

• Proencephalon (forebrain)
• Mesencepholon (midbrain)
• Rhombencephalon (hindbrain)

Question 6

5 brain vesicles?

Answer 6

Proencephalon

• > Telencephalon
• > Diencephalon

Mesencephalon

Rhombencephalon

• > Metencephalon
• > Myelencephalon

Question 7

Oligo-2 positive cells -FACS->?

Answer 7

neurons OR astrocytes

Question 8

What is the order of formation of Oligo2 +ve cells?

Answer 8

Neurons, THEN astrocytes

Question 9

Experimental evidence of Oligo2 +ve cell formation.

Answer 9

Mouse

E9.5 days -> neurons and astrocytes

E13.5 days -> astrocytes

Question 10

How neuron VS glial fate choice is regulated (AND some examples) ?

Answer 10

• temporal + spatial regulation by expression of G.Factors and T. Factors
• competing for shared components in signalling pathways (STAT 3 phosphorylation pathway)
• epigenetic regulation of neuron/glial differentiation (methylation of binding site for phosph-STAT3)

Question 11

Neurogenin promotes _____and inhibits_____

Answer 11

Neurogenin promotes neurogenesis and inhibits glial cell differentiation (by other mechanisms)

Question 12

RODENT SVZ: NSC self renewal pathway?

Answer 12

SVZ NSCs migrate down Rostral Migratory Stream and integrate into Olfactory bulb (smell is important)

Question 13

What do the LIF pathway and Ngn pathways compete for?

Answer 13

STAT-3 phosphorylation pathway

Question 14

Targets for the STAT-3 phosphorylation pathway?

Answer 14

GFAP: for glial differentiation (astrocytes)

NeuroD: for neuronal differentiation

Question 15

Region(s) where NSCs are located (in adult brain)?

Answer 15

sub-ventricular zone (SVZ) and the sub-granular zone (SGZ) of the hippocampal dentate gyrus

NB: these NSCs can form all types of neuronal cell, but have a more glial identity

Question 16

HUMANS: NSC self renewal (in SVZ) pathway?

Answer 16

Neuronal stem cells (astrocyte-like) Type B

|

Type C rapidly dividing transit amplifying cells

|

Migrating neuroblast (Type A)

|

Migration (to mature into interneurons in olfactory bulb)

Question 17

Factors that influence NSC niche?

Answer 17

Cellular Elements

• astrocyte
• endothelial
• ependymal

Molecular Signals
- VEGF
- FGF
- EGF
- BDNF
- SHH
etc

Question 18

NSC self-renewal in the hippocampus

Answer 18

NSC in the sub-granular dentate gyrus

|

Progenitor cells

|

Immature neurons

|

Migration into the granule cell layer

|

Integration axons inti CA3 region dendrites in the molecular layer ]- FOR LEARNING AND MEMORY

Question 19

NSC from SGZ to SVZ–> ?

NSC from SVZ to SGZ–> ?

Answer 19

NSC from SGZ to SVZ–> olfactory bulb

NSC from SVZ to SGZ–> new neurons in the dentate granule cell layer

Question 20

Other structures in the SVZ?

Answer 20

Blood vessels and endothelial cells:

• basal lamina
• ependymal cells

Question 21

How to convert fibroblast -> neurons

Answer 21

Use key t. factors for interneurons

Mash1
Brn2
Mytl1

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