stem cell disorders

Question 1

where are neural stem cells found in development

Answer 1

neural stem cells are found lining the ventricles

Question 2

flow of cell types to neurons

Answer 2

neuroepithelial cells (lining the ventricles) –> radial glial cells –> intermediate progenitor cells –> neurons/astrocytes/oligodendrocyte progenitor cells

Question 3

radial glial cells

Answer 3

scaffolding for migrating neurons in developing brain

progeny migrates up fibres and remain in column

Question 4

mouse vs human brain

Answer 4

size
mouse brain lissencephalic
cell types: ventricular radial glial cells present in both. Outer radial glial cells only in humans

Question 5

how are neuroepithelial cells (vRGs) formed

Answer 5

they self-renew to make more
do this through vertical division plane

same thing when making neurons (vertical division plane)

Question 6

how are outer radial glial cells made

Answer 6

radial glial cells generate oRGCs by undergoing horizontal division

the progeny in contact with the ventricle remains a radial glia while the other cells become oRGCs

oRGs create progeny through mostly horizontal divisions

Question 7

layers of developing cortex

Answer 7

ventricular zone (vRG)
inner subventricualr zone (progenitor cells)
outer subventriciular zone (oRGs)

Question 8

inside out development of the cortex

Answer 8

brain first makes neurons closest to ventricle, next batch migrate through those cells and position above them

Question 9

neurogenesis in adult dentate gyrus

Answer 9

dentate gyrus is part of hippocampus
NSCs are radial glial-like cells
multipotent NSCs and usually quiescent

Question 10

3D culture human neurons

Answer 10

brain organoids, derived from IPS cells

all layers of developing cortex
no vascular system –> necrotic core

Question 11

Seckel syndrome

Answer 11

autosomal recessive congenital disorder
centrosomal-P4-1-associated protein

intellectual disability, short build, decrease blood cells, microcephaly

Question 12

CPAP mutation in Seckel syndrome leads to

Answer 12

thinner ventricular zone (fewer neural stem cells)

disrupted division plane (may impact generation oRGCs)

Question 13

how does Zika virus cause microcephaly

Answer 13

induces cell death of NSCs
reduces NSC proliferation by ventricle

–> reduced thickness of ventricular zone and neuronal layer

Question 14

RAB39b-PI3K-mTOR pathway mutation

Answer 14

overproliferation NPCs
thinner ventricular zone
disrupted differentiation
–> macrocephaly

Question 15

miller-dieker syndrome

Answer 15

deletion 17P13.3
autosomal dominant
lishencephaly