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Developmental Neuroscience > Wiring Eye to Brain > Flashcards

Wiring Eye to Brain Flashcards

1
Q

3 main functions of growth cones

A

guidance
extension of neurite
form pre-synaptic element

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2
Q

RGC and netrin

A

attracted and later repelled

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3
Q

2 ways to study guidance mechanisms

A

expression analyses

culture approaches

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4
Q

expression analyses

A

receptors expressed by neurons

ligands along path - present at right time?

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5
Q

culture approaches

A

axon respond to signalling molecule? changes in rate and direction of growth

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6
Q

why is optic projection ideal model for studying guidance mechanisms?

A

formed by axons of single neuronal type - RGC
accessible
navigated via intermediate targets

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7
Q

3 important signalling molecules

A

robos/slits, ephs/ephrins and neuropilins/sema/vegf

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8
Q

robos

A

receptors

1-4

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9
Q

slits

A

ECM molecules
usually inhibit axon outgrowth
slit 1-3
little receptor specificty

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10
Q

Ephs

A

receptor
tyrosine kinases
ephA bind ephrin A and EphB binds Ephrin B

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11
Q

ephrins

A

cell surface associated molecules - inhibitory

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12
Q

ephrins - reverse signalling

A

ephrins can be receptors and ephs as ligands

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13
Q

neuropilin + flk1/flt1 co-receptors

A

VEGF

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14
Q

neuropilin + plexins co-receptors

A

class 3 semaphorins

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15
Q

growth into OFL

A

cells divide, cell bodies of RGC migrate up to RGC layer and extend into OFL

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16
Q

attraction and repulsion - growth into OFL

A

attraction of OFL ECM

repulsion from outer retina

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17
Q

Molecules help to repulse RGC from OFL

A

slit/robo

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18
Q

Where are slits expressed and what to RGC express?

A

slit 1 and 2 in inner retina

RGC express robo 2

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19
Q

mice lacking slit 1/2 - Where do RGC grow?

A

outer retina - not all but a subset of axons make mistakes - other important molecules

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20
Q

growth to optic dis - robo/slit

A

KO slit 1/2 = axons grow disorganised
some grow peripherally then to optic disc
initial polarity lost

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21
Q

What attracts neurons centrally to optic disc?

A

shh

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22
Q

shh expression pattern in retina

A

low peripheral and high retina

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23
Q

what is required for growth out of eye?

A

netrin/DD signal

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24
Q

where is netrin expressed in optic disc?

A

by glia

25
Q

What axons express DCC

A

retinal axons

26
Q

no netrin

A

axons fail to exit eye

small optic nerves

27
Q

binocular disparity

A

image projected on each eye slightly differently

28
Q

what is size of ipsilateral projection related to?

A

degree of binocular overlap in visual field

29
Q

binocular overlap human vs mice

A

human 55:45

mouse 97:3

30
Q

where do ipsilateral axons always arise from?

A

temporal retina

31
Q

albinism and guidance at optic chiasm

A

50% fewer ipsilateral axons

lack of melanin in RPE

32
Q

non-decussating retinal fugal fibre syndrome

A

no chiasm, very rare

33
Q

robos/slit path defining

A

expressed around RGC and absent from regions where they grow
barrier function

34
Q

no slit 1,2 - optic chiasm

A

cross in wrong place, grow into other nerve, wander away from path

35
Q

what helps axons project contralaterally at chiasm?

A

NRP1-VEGFA

36
Q

marker of contralaterally projecting neurons?

A

NRP1

37
Q

mice lacking NRP1 - crossing at midline

A

many axons fail to cross the midline

38
Q

3 VEGF isoforms

A

VEGF 188, 164 and 120

39
Q

differences between VEGFA isoforms

A

exon 6 and 7

40
Q

importance of exon 6 and 7 in vegf a

A

influence neuropilin binding

41
Q

isoform VEGFa receptors

A

flt1,flk1 and NRP1/2

42
Q

what vegfa isoform has exon 6 and 7

A

188

43
Q

cant KO VEGFA in animal models - what is done?

A

use VEGF120 as no exon 7 for NRP1

44
Q

main NRP1 ligand in nervous system

A

sema3

45
Q

is sema3 required for axon crossing at chiasm?

A

no

46
Q

Mice lacking VEGFA/NRP1 - chiasm

A

many RGC axons fail to project contralaterally

47
Q

does VEGFA attract or repel growth cones?

A

attract

48
Q

Effect of KO NRP1 in RGC and epithelial cells

A

RGC - axons go ipsilaterally

no effect on epithelial cells

49
Q

What stops ipsilateral crossing?

A

lack NRP1

ephrins/ephs

50
Q

xenopus - stage specific ephrin B at midline

A

lateral - eyes completely crossed projection, no ephrin B
binocular vision - ephrin B at midline
ephB in tadpole - precocious ipsilateral projection

51
Q

Is ephrin B necessary for ipsilateral growth?

A

yes - EphBs expressed by ipsis
no ephb1 = fewer ipsis
ephB2 expressed at chiasm
no ephB2 = fewer ipsis

52
Q

what specifies ipsilateral RGCs?

A

zic2

53
Q

zic2 in fish/humans

A

none in fish - crossed

binocular species - zic2 in region that gives rise to ipsis

54
Q

in utero electroporation

A

tease embryo out of uterus
inject DNA
use small electric current to drive DNA into tissue of interest

55
Q

what happens when zic 2 electroporated?

A

drive cells ipsilaterally in optic chiasm

56
Q

what does zic2 do to ephb1?

A

induces expression

57
Q

which is expressed first - zic2 or ephb?

A

ephb

58
Q

electroporate zic2 into central retina in ephb1 KO mice

A

size of ectopic ipsilateral tract decreased substantially

Developmental Neuroscience (10 decks)

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