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332: Neurobiology > 9. Neural Development > Flashcards

9. Neural Development Flashcards

1
Q

where does neural stem cell replication occur

A

in the ventricular zone of the neural tube

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2
Q

for a neuroepithelial cell to produce radial glia, what genes must it be under the influence of

A

either:
FOXG1
HX2
PAX6

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3
Q

what are radial glia used for

A

neuronal migration

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4
Q

where does the neural tube begin closing up

A

in the middle (think of it like a burrito)

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5
Q

what are the openings of the neural tube called

A

anterior and posterior neuropores

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6
Q

which neuropore of the neural tube closes up first

A

the anterior neuropore closes on day 25
the posterior neuropore closes on day 27

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7
Q

what are somites

A

bilaterally paired blocks of mesoderm that form along the head-to-tail axis

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8
Q

what signalling molecule determines the anterior-posterior axis

A

Wnt

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9
Q

what is Wnt signalling role in the dorsal-ventral axis

A

Wnt specifies the Nieuwkoop centre by allowing beta-catenin release and translocation

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10
Q

name 3 Wnt inhibitors

A

dickkopf
cerberus
insulin-like growth factor

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11
Q

what are Wnt inhibitors also known as

A

paracrine factor antagonists

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12
Q

what produces Wnt inhibitors, why?

A

the organiser and dorsal anterior mesoderm

this allows neuroectodermal tissue to be established

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13
Q

what is the evidence for the role of Cerberus in allowing neuroectoderm development

A

ectopic placement of Cerberus during early gastrulation produces a secondary head structure

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14
Q

where is Wnt found in high concentrations

A

the ventral, posterior aspect

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15
Q

what 2 molecules are important in anterior-posterior patterning

A

fibroblast growth factor (FGF)
retinoid acid

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16
Q

where is fibroblast growth factor found in high concentrations

A

in the posterior end
(it is degraded at the anterior)

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17
Q

where is retinoic acid found in high concentrations

A

high concentrations in the middle of the embryo

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18
Q

where is retinoid acid made

A

by the central mesoderm

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19
Q

what do FGF, RA and Wnt signalling all regulate

A

Hox gene expression - these genes act as positional cues

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20
Q

what two gradients control torso-ventral patterning

A

Wnt and TGF-beta

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21
Q

describe what happens to dorsal neurons of the spinal cord

A

high Wnt signalling instructs them to become sensory neurons

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22
Q

describe what happens to ventral neurons of the spinal cord

A

low concentrations of Wnt signal to them to become motor neurons

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23
Q

what happens to the anterior part of the neural tube in the first stages of brain development

A

the anterior part divides to form three primary vesicles:
the forebrain, midbrain and hindbrain

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24
Q

what happens to the forebrain? what does it go on to form?

A

it curls up to form a three pronged structure that develops into the cerebral cortex

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25
Q

what happens to the posterior part of the neural tube

A

it forms the spinal cord

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26
Q

what does the midbrain go on to form

A

vision, hearing and motor control

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27
Q

what does the hindbrain go on to form

A

the medulla, pons and cerebellum

28
Q

how many layers is there in the cerebral cortex

A

6

29
Q

what is the internal and external layer of the cerebral cortex

A

the external layer is the molecular layer

the internal layer is the fusiform layer

30
Q

describe pyramidal neurons

A

cell body is a triangular shape
they have extensive up reaching dendrites
typically glutamatergic neurons

31
Q

describe the movement of the first cohort of post-mitotic neurons

A

moves up from the ventricular zone towards the pial surface to form the preplate

32
Q

how do post-mitotic neurons get transported

A

across the radial glial cell scaffold

33
Q

the first wave of neurons arrive in the prelate, what then happens?

A

the prelate is split into three zones:
1. marginal zone
2. cortical plate
3. subplate

34
Q

what do neural stem cells produce

A

nestin

35
Q

cortical plate neurons arrive in an inside out sequence, what does this mean?

A

the earliest born neurons become layer 6
and the last to arrive become layer 2

36
Q

how can we visualise neural stem cells

A

using an anti-nestin antibody

37
Q

what type of protein is nestin

A

an intermediate filament protein

38
Q

what do immature glial cells (including radial glial cells) produce

A

vimentin

39
Q

how can we visualise radial glial fibres

A

using aan anti-vimentin antibody

40
Q

how do neurons migrate towards the target area

A

they detach from radial glia and can translocate tangentially to their final position

41
Q

what is reelin

A

an extracellular matrix-associated glycoprotein

42
Q

what type of cells secrete reelin

A

cajal-retzius cells

43
Q

where are cajal-retzius cells found

A

in the marginal zone

44
Q

where is reelin secreted by the cajal-retzius cells

A

cajal-retzius cells have ascending processes which contact the pial surface and secrete reelin

45
Q

name 2 receptors reelin binds to

A

very low density lipoprotein receptor (VLDL-R)
apolipoprotein E receptor type 2 (ApoER2)

46
Q

what happens once reelin binds to the receptor

A

disabled 1 binds to the cytoplasmic tail of the receptor and gets phosphorylated

downstream kinase signalling results in gene expression that drives migratory behaviour

47
Q

what happens in reeler and scrambler mice

A

the preplate fails to split because new neurons are unable to penetrate into it

48
Q

what are reeler and scrambler mice

A

mice that are null for reelin and disabled 1

49
Q

what is human reelin mutation linked to

A

lissencephaly and autism

50
Q

how can you visualise preplate neurons

A

staining with chondroitin sulphate proteoglycans

51
Q

some stem cells are retained in the human brain, give 2 examples

A

dentate gyrus stem cells involved in memory
doublecortin - expressed by immature neurons

52
Q

what part of disabled 1 becomes phosphorylated

A

the phosphotyrosine interacting domain

53
Q

after Dab1 is phosphorylated, what can it now do

A

bind to protein tyrosine kinases Src, Abl and Fyn

54
Q

what happens in mutations of the doublecortin gene

A

defective migration of neurons results in poorly organised layers of the cortex

= double cortex syndrome or lissencephaly dependent on gender

55
Q

why does the pathology associated with doublecortin mutations depend on gender

A

DCX gene is located on the X chromosome, so females have half a functional copy of the gene that results in half the cells migrating correctly, the others do not
= double cortex syndrome

no functional copy of the DCX protein = lissencephaly

56
Q

how is doublecortin implicated in cancer metastasis

A

unstable interaction between DCX and microtubules destabilises the cellular organisation = disorganised cell movement

57
Q

what is doublecortin

A

a microtubule associated protein

58
Q

where is doublecortin expressed

A

in migrating neurons of the CNS and PNS during embryonic and postnatal development

59
Q

why do neural crest cells become peripheral neurons and ganglia

A

because they have a low affinity for neurotrophic p75 receptor

60
Q

what produces radial glia progenitor cells

A

neuroepithelial stem cells

61
Q

where do neural stem cells develop from

A

the ventricular zone of the neural tube

62
Q

name 3 things neural stem cells go on to produce, which first

A

neurons
astrocytes
oligodendrocytes

63
Q

what is the role of SOX2
what happens if there is a loss of SOX2

A

maintaining neural stem cells
loss of SOX2 = causes the cell to exit the cell cycle

64
Q

what is the role of SOX1 and SOX3

A

regulate neural progenitor cell states

65
Q

why is there not many stem cells in the adult brain

A

332: Neurobiology (15 decks)

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