Neuronal Stem Cells (NSC) in the Central Nervous System (CNS) Flashcards
Define self renew
Capacity to proliferate to produce multiple cells
Define multipotent
capacity to differentiate to produce major cell lineages (e.g. neurons, astrocytes)
Neural plate forms at __ weeks gestation
Neural plate forms at 3 weeks gestation
Where do PNS cells arise from?
Neural Crest
3 Brain vesicles formed from the closure of the rostral neuropore?
- Proencephalon (forebrain)
- Mesencepholon (midbrain)
- Rhombencephalon (hindbrain)
5 brain vesicles?
Proencephalon
- > Telencephalon
- > Diencephalon
Mesencephalon
Rhombencephalon
- > Metencephalon
- > Myelencephalon
Oligo-2 positive cells -FACS->?
neurons OR astrocytes
What is the order of formation of Oligo2 +ve cells?
Neurons, THEN astrocytes
Experimental evidence of Oligo2 +ve cell formation.
Mouse
E9.5 days -> neurons and astrocytes
E13.5 days -> astrocytes
How neuron VS glial fate choice is regulated (AND some examples) ?
- 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)
Neurogenin promotes _____and inhibits_____
Neurogenin promotes neurogenesis and inhibits glial cell differentiation (by other mechanisms)
RODENT SVZ: NSC self renewal pathway?
SVZ NSCs migrate down Rostral Migratory Stream and integrate into Olfactory bulb (smell is important)
What do the LIF pathway and Ngn pathways compete for?
STAT-3 phosphorylation pathway
Targets for the STAT-3 phosphorylation pathway?
GFAP: for glial differentiation (astrocytes)
NeuroD: for neuronal differentiation
Region(s) where NSCs are located (in adult brain)?
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
HUMANS: NSC self renewal (in SVZ) pathway?
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)
Factors that influence NSC niche?
Cellular Elements
- astrocyte
- endothelial
- ependymal
Molecular Signals - VEGF - FGF - EGF - BDNF - SHH etc
NSC self-renewal in the hippocampus
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
NSC from SGZ to SVZ–> ?
NSC from SVZ to SGZ–> ?
NSC from SGZ to SVZ–> olfactory bulb
NSC from SVZ to SGZ–> new neurons in the dentate granule cell layer
Other structures in the SVZ?
Blood vessels and endothelial cells:
- basal lamina
- ependymal cells
How to convert fibroblast -> neurons
Use key t. factors for interneurons
Mash1
Brn2
Mytl1
[THIS WAS SUCCESSFUL]
