Topic 3 Neurovascular Development

Question 1

name the brain barriers

Answer 1

the meninges - dura mater, arachnoid mater, pia mater
blood brain barrier
blood cerebrospinal fluid barrier

Question 2

list features of BBB

Answer 2

Tight junctions (no paracellular transport)
low rates of transcytosis
non-fenestrated
lipophillic cross BBB

Question 3

what are angioneurins?

Answer 3

several families of shared molecular guidance cues that guide both endothelial cells and neurons

Question 4

what cells does the neural tube recruit on E8.5 when the neural tube is avascular?

Answer 4

angioblasts - endothelial cell precursors

Question 5

what happens after the recruitment of angioblasts

Answer 5

this is the vasculogenesis of the neural tube, the formation of the perineural vascular plexus (PVNP)

Question 6

what do Neural progenitor cells secrete to attract angioblasts?

Answer 6

VEGF-A

Question 7

what two signalling molecules/pathways are needed for blood vessel ingression into the neural tube

Answer 7

Wnt7 and VEGF-A signalling needed to form the Intraneural Vascular Plexus (INVP)

Question 8

what do radial glial cells express in hypoxic and poorly-vascularized environments

Answer 8

HIF1-alpha

Question 9

what does HIF1-ALPHA trigger

Answer 9

glycoloysis and RGC proliferation

Question 10

how does vascularization impact HIF1-alpha expression

Answer 10

oxygenation via vascularization will suppress HIF1-alpha expression

Question 11

what do Tip cells extend to directly contact RGC and what does this do?

Answer 11

the Tip cells from ingrowing blood vessels contact the RGCs via extension of filopodia, this prolongs the mitotic phase of cell division in RGCs and favours early neuronal differentiation

Question 12

Wnt signalling from neurons to endothelial cells promotes expression of ?

Answer 12

B-catenin

Question 13

what do endothelial cells secrete to mediate pericyte recruitment?

Answer 13

ECs secrete PDGF-BB which interacts with PDGFR-beta in pericytes which induces pericyte recruitment

Question 14

what do astrocytes release to act on endothelial patched homolog 1 (PTC-1) to contribute to BBB formation

Answer 14

astrocytes release sonic hedgehog which acts on endothelial PTC-1 receptor, this elicits signalling to contibute to BBB formation

Question 15

what do endothelial cells secrete to contribute to proper neurovascular patterning?

Answer 15

endothelial cells secrete VEGF and IGF-1 which contributes to proper neurovascular patterning

Question 16

describe the vascular-guided migration of oligodendrocyte precursors

Answer 16

OLPs are guided by the vasculature
OLPs secrete Wnt which acts in an autocrine manner to induce expression of CXCR4
ECs secrete CXCL12 (the ligand for CXCR4) to attract OLPs and sustain their undifferentiated state.

Question 17

maturation of oligodendrocytes is accompanied by:

Answer 17

downregulation of Wnt expression, as well as CXCR4

Question 18

where are new neurons continuously generated postnatally?

Answer 18

in the SVZ

Question 19

which interneurons require vascular guidance for migration

Answer 19

GABAergic neurons have receptors for GABA which is secreted by blood vessels

Question 20

what does Wnt signal from neurons to endothelial cells

Answer 20

to produce B-catenin which promotes BBB specific genes

Question 21

what do ECs secrete

Answer 21

endothelial cells secrete PDGF-BB

Question 22

where are the receptors for PDGF-BB located

Answer 22

on pericytes

Question 23

what do astrocytes secrete which acts on PTC-1 recepotr

Answer 23

astrocytes released SHH which acts on endothelial patched homolog 1 receptor, elicits signalling that contributes to the BBB formation

Question 24

what do endohelial cells secrete that contributes to proper neurovascular patternin?

Answer 24

IGF-1 and VEGF