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ICB- developmental biology > developmental biology of the brain > Flashcards

developmental biology of the brain Flashcards

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1
Q

what is gastrulation?

A

the process where the single layered blastula is reorganised into a trilaminar structure called the gastrula

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2
Q

describe the framework for CNS development

A
  • rapidly dividing ball of cells
  • signalling centres develop
  • cell mixing restricted
  • cells destined to be skin or brain
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3
Q

once a cell is destined to be neural tissue what occurs?

A
  • neurones are generated and they migrate to final position
  • glia are produced
  • synapses are generated
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4
Q

how many glia are there per neurones?

A

there are 10 times as many glia cells than neurones

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5
Q

once synapses are generated in the CNS what occurs?

A

excess neurons are culled

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6
Q

what occurs in the CNS throughout life?

A

fine tuning

new synapses are formed and neurones are tested to see whether they need to be maintained

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7
Q

what is the neuroectoderm?

A

it is ectoderm which received bone morphogenetic protein-inhibiting signals from proteins such as noggin, which leads to the development of neural tissue (and not skin)

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8
Q

where do the signal to the ectoderm (to become neuroectoderm) come from?

A

the axial mesoderm, which is ideally placed under the ectoderm for signalling

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9
Q

what ensure correct neural plate formation? (3)

A
  • signals expressed in correct location
  • signals that are produced have the correct cell type inducing ability
  • signals expressed at the correct time
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10
Q

what is BMP4?

A

bone morphogenetic protein 4 is a pro-epidermis and anti-neutralising signal
by default all ectoderm will become skin
this needs to be blocked to form neural tissue

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11
Q

what signals block BMP4? (4)

A
  • Cerberus
  • chordin
  • noggin
  • follistatin
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12
Q

what is the proposed retinoic acid concentration gradients function?

A

anterior/posterior signalling

high concentration at the head and low at the tail

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13
Q

what signals need to be inhibited to make a head? (3)

A
  • Wnt/B-catenin
  • TGF
  • BMP
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14
Q

what is the neural plate?

A

neutrally committed, multipotent stem cells

TF expressed are that of a broad domain, restricting cell potency

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15
Q

why might making a nock-out mouse for a specific TF in neuronal differentiation not make an effect?

A

the brain is robust, there is lots of redundancy that will compensate for the lack of TF

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16
Q

what TF maintain neural progenitor from differentiating?

A

Sox 1, 2 and 3

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17
Q

which sox gene is important in fate switching?

A

Sox2 in neural ectoderm inhibits Oct4

Oct4 drives the formation of mesoderm

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18
Q

what is sox2 also important for?

A

localisation of the stomach in the gut

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19
Q

Additionally, what is the function of other sox TFs?

A

to stop stem cell like proliferation and drive neural differentiation

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20
Q

along with special and temporal factors, what else effects gene expression?

A

gender

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21
Q

why are mouse embryos hard to work with?

A

they are hard to culture and need to be looked after

can be cultured for a few days in a bioreactor

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22
Q

what can be done to a chick to observe the effect of a TF on nervous system development?

A

electrophorese a gene into the side of embryo through a window of an egg
the other side of the embryo can be used as a control

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23
Q

why are in utero operations difficult?

A

can easily trigger a miscarriage

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24
Q

why are Xenopus embryos useful in developmental studies?

A

embryos are quite large and easy to manipulate

this means they are useful in telling us about the early stages of development

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25
Q

how can the same set of morphogens used in different parts of the embryo produce different tissue?

A

these signals are acting on cells with different TF profiles. for example, response gene for a signal may be so epigenetically repressed, from a past signal, that there is no response.

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26
Q

what happens if neural stem cells are triggered to leave the cell cycle too early by manipulating factors regulating the cell cycle?

A

brain formed is too small

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27
Q

what happens if neural stem cells are artificially kept in the cell cycle for too long before leaving?

A

lots of neurones will end up being culled

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28
Q

how have humans tweaked the cell cycle in the cerebral cortex over evolution?

A

increased proliferation before differentiation

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29
Q

what does the notochord release to induce the anterior/posterior regionalisation of the neural tube?

A

Shh

30
Q

what are bHLH? and what do they do?

A

a group of pro-neural TFs, they tell neural stem cells to make neurones

31
Q

what is neurogenin?

A

a family of bHLH TFs involved in neuronal differentiation

32
Q

name a localised TF for retinal development

A

bHLH Ath5

33
Q

what does oscillations of bHLH TFs maintain?

A

multipotency

34
Q

what happens when there bHLH TFs are stably expressed?

A

differentiation

35
Q

name a pro-neural gene involved in cerebellum development

A

math1

FISH can be used to located this marker in early embryonic development

36
Q

in what order are the brain axes formed?

A
  • anterior/posterior
  • dorsal/ventral
  • left/right
37
Q

at what point is the DV axis established

A

shortly after neural tube closure

38
Q

what are the three main regions of the brain?

A
  • hindbrain
  • midbrain
  • forebrain
39
Q

what do signalling centres release?

A

local signals/morphogens

40
Q

name an example of a signalling centre, giving its location

A

the isthmus is a signalling centre located at the midbrain/hindbrain boundary

41
Q

what will the hindbrain become?

A

the cerebellum

42
Q

where are dopaminergic neurones located?

A

in the midbrain at the bottom of the neural tube, they project into the forebrain in later development

43
Q

what happens when you move the location of a signalling centre?

A

trigger development of the different tissues in the wrong part of the brain

44
Q

name the two key signals released from the isthmus?

A

FGF8 and Wnt1

45
Q

what occur in Oct2 null mice?

A

they lack anything in front of the isthmus (brain anterior)

46
Q

what causes DN apoptosis in Parkinson’s?

A

the production of ROS

47
Q

what signals the ventral location of dopaminergic neurones?

A

Shh

48
Q

what signals the midbrain information of dopaminergic neurons?

A

FGF8 and Wnts

49
Q

what is the substantia nigra?

A

it is the location of DN in the midbrain

it is diminished in Parkinson’s

50
Q

what happens when SNpc DN die?

A

tremors and reduced movement

this occurs in Parkinson’s

51
Q

what is the function of VTA DN?

A

they are involved in mood control and addition

they are not affected in Parkinson’s

52
Q

what are radial glia?

A

they are neuronal stem cells that can form DN and later astrocytes to support DN

53
Q

what are astrocytes?

A

star shaped glial cells of the CNS

54
Q

what’s the additional function of radial glial?

A

act as scaffold for DN to migrate along

DN exit the cell cycle in the ventricular zone and migrate down RG to ventricle edge

55
Q

what does cortical hem secrete?

A

Wnts and BMP

56
Q

what does cortical anthem secrete and why?

A

extracellular region of Frizzled recepts, this binds wnt and locally prevents Wnt signalling

57
Q

control of cell type and number is important. which additional factor is especially important in the layered cortex

A

migration

58
Q

which two cell types are important for this migration?

A

radial glia and Cajal-retzius cells

59
Q

what is the function of Cajal-retzius cells?

A

they are not entirely understood but seen to be essential in stopping cell migration

60
Q

what is microcephaly?

A

congenital condition associated with incomplete brain development

61
Q

which virus is suggested to be causing microcephaly?

A

Zika virus

this is additionally associated with additional neuronal cell death and even fewer neurons

62
Q

what is used to model microcephaly and show links to Zika?

A

cerebral organoids

these have organisation much like the cerebral cortex

63
Q

what causes reduced neurone production in microcephaly?

A

incorrect spindle orientation resulting in not enough symmetrical division of radial glia

64
Q

how many layers are there in the neocortex?

A

6

they are not completely independent and need to be in the correct order for function

65
Q

what percentage of neurones in the neocortex are excitatory? name the one type that is inhibitory

A

80%

GABA interneurons

66
Q

which layer of the cortex is generated first?

A

the deepest layer

newly generated neurones crawl past these to form upper layers towards meninges membrane guided by radial glia

67
Q

what causes lissencephaly?

A

a disorder of cortical migration caused by cells not responding correctly to signals and dysfunctional cytoskeletons, resulting in missing/disordered layers of the cortex

68
Q

what is reelin?

A

protein released by Cajal-retzius cells signalling cells to migrate toward these cells

69
Q

what recent discovery was made about oligodendrocytes using single-cell RNA-seq?

A

there are 5 types of oligodendrocytes (cells which myelinated neurones), these are the cells which are attacked in MS

70
Q

what causes radial glia cells to produce astrocytes and not DN?

A

methylation of pro-neural genes histones

71
Q

what is the Blue Brain Project?

A

they are trying to map the human connectome in order to be able to engineer a novel system

ICB- developmental biology (5 decks)

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