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Neuro Development and Disease > Migration and Axonal Pathfinding > Flashcards

Migration and Axonal Pathfinding Flashcards

1
Q

What do neural stem cells in the SVZ do?

A

proliferate to generate new neuroblasts

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2
Q

Where do neuroblasts migrate?

A

rostrally along the rostral migratory stream to the olfactory bulb

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2
Q

What are neuroblasts?

A

precursors of neurons during embryonic development

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3
Q

What do neural progenitor cells give rise to?

A

many glial and neuronal cell types of the CNS

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3
Q

What is neurogenesis?

A

the process by which new neurons are formed in the brain

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4
Q

What is gliogenesis?

A

the generation of glial cells (non-neuronal cells) in the nervous system

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5
Q

What happens to neurons generated by self-renewing neuroepithelial cells?

A

they are transformed into radial glial cells

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6
Q

What do radial glia cells produce?

A

intermediate progenitor cells and oligodendrocyte precursor cells (OPCs)

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7
Q

What do intermediate progenitor cells and OPCs produce respectively?

A
  • intermediate progenitor = neurons
  • OPCs = oligodendrocytes
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8
Q

What can radial glia become?

A
  • astrcoytes
  • astrocytic progenitors
  • ependymal cells
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9
Q

What do type B cells in the cortical SVZ produce?

A

transit-amplifying cells (type C cells), which in turn produce OPCs and neurons

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10
Q

What is corticogenesis?

A

the process during which the cerebral cortex of the brain is formed

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11
Q

What does the neocortex comprise?

A

the largest part of the cerebral cortex and approximately half the volume of the human brain

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12
Q

What is the neocortex responsible for?

A

the neuronal computations of attention, thought, perception and episodic memory

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13
Q

How many layers does the neocortex have?

A

6 (I is most superficial and VI is the deepest)

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14
Q

What is the pial surface of the brain?

A

the interface between the surface of the brain and the surrounding meninges

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15
Q

What are the 2 major cortical neuronal populations?

A
  • cortical projection neurons
  • cortical interneurons
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16
Q

What are cortical projection neurons and where do they come from?

A

excitatory in nature (glutamatergic) that account for ~80% of all cortical neurons that come from cortical proliferative areas

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17
Q

How do cortical projection neurons migrate?

A

radially to the cortical plate through the intermediate zone

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18
Q

What are cortical interneurons and where do they come from?

A

inhibitory in nature (GABAergic) that come from the medial ganglionic eminence

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19
Q

What can cortical interneurons do?

A

mediate feedforward inhibition, feedback inhibition, volume transport, and disinhibition

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20
Q

What are the 2 modes of cortical interneuron migration?

A
  • radial (follow a track that is perpendicular to the neuroepithelial surface)
  • tangential (parallel to the pial surface)
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21
Q

What is Somal translocation mediated by?

A

MTs in the neuron

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22
Q

What are the 3 steps of somal translocation?

A
  1. leading process extends as driven by MT extension
  2. centrosome moves forward into the leading process while trailing end of the cell contracts
  3. nucleus moves forward toward the centrosome and the trailing process retracts
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23
Q

What is radial migration mediated by?

A

the radial glia during locomotion

24
Q

What are the 5 steps of radial migration?

A
  1. generation of newborn cortical neurons
  2. multipolar tangenital migration
  3. multipolar-unipolar transition
  4. attachment and locomotion
  5. detachment
25
Q

What are cadherins?

A

calcium dependent homophilic molecules

26
Q

What does N-cadherin do during corticogenesis?

A

facilitate radial migration by enabling cell-to-cell adhesion between migrating neurons and radial glial fibres

27
Q

What is cortical migration coordinated by?

A
  • intrinsic factors e.g. actins, tubulins, RhoA, dynein, myosin II
  • extrinsic factors e.g. Reelin, ephrins, RA, Wnt
28
Q

How do the extrinsic and intrinsic factors that control cortical migration affect the cytoskeleton?

A

by binding to cell surface receptors to induce changes e.g. polymerisation of tubulin and actin

29
Q

What is Reelin?

A

a secreted ECM glycoprotein produced by Cajal-Retzius cells in the marginal zone that promotes migration along and/or detachment from radial glia cells

30
Q

What do migrating neurons express?

A

Reelin receptors ApoER2 (Apolipoprotein E receptor 2) and VLDLR (Very low-density lipoprotein receptor)

31
Q

What is a key adaptor protein in Reelin signalling?

A

Disabled-1 (Dab1)

32
Q

What have autosomal recessive mutations in the RELN gene been linked to?

A

developmental disorder Lissencephaly 2 with brain malformation

33
Q

What does neuronal maturation lead to?

A

neuronal polarisation

34
Q

What is neuronal polarisation?

A

the formation of axons and the separation of the axonal and somatodendritic domains

35
Q

What is axonal pathfinding?

A

the process of how an axon finds its target

36
Q

What are the 2 principal events that take place in the in vitro system of axonal pathfinding?

A
  1. growth of neurites
  2. establishment of neuronal polarity
37
Q

What are the 5 steps of neuronal differentiation in vitro?

A
  1. neuritogenesis
  2. neurite outgrowth
  3. pathfinding
  4. targeting
  5. synaptogenesis
38
Q

Where does neuritogenesis occur during neuronal differentiation?

A

at thin, actin rich peripheral protrusions surrounding the soma

39
Q

What drives neurite outgrowth and pathfinding?

A

the growth cone (tip of the axon)

40
Q

What are the 2 domains of the growth cone?

A
  • central (C) domain that contains MTs
  • peripheral (P) domain that contains F-actin in filopodia and lamellipodia
41
Q

What are filopodia and lamellopodia made up of respectively?

A
  • filopodia = bundles of longer F-actin
  • lamellipodia = randomly oriented networks of shorter F-actin between the filopodia
42
Q

What is the assembly and disassembly of F-actin orchestrated by?

A

a variety of actin-binding proteins that function downstream of Rho-family GTPases

43
Q

What does profilin do?

A

promote actin assembly at the barbed end

44
Q

What is CapZ?

A

a barbed-end capping protein that prevents F-actin elongation

45
Q

What is WASP/Scar?

A

activator of Arp2/3 complex

46
Q

What does the Arp2/3 complex do?

A

initiate new F-actin as a branch on the side of an existing filament

47
Q

What does ADF/cofilin do?

A

stimulate F-actin depolymerisation and debranching at the pointed end (actin severing protein)

48
Q

What regulates actin dynamics during neuritogenesis?

A

LIM kinase 1 and cofilin

49
Q

What does an increase in intracellular cAMP conc by activation of AC trigger?

A
  1. increased LIM kinase 1 expression
  2. novel expression of VDCCs
50
Q

What are the effects of an increase in LIM kinase 1?

A
  • cofilin phosphorylation which abolishes its ability to bind and depolymerise actin
  • this promotes polymerisation of actin monomers which induces neuritogenesis
51
Q

What does novel expression of VDCCs do?

A
  • negatively regulate LIM kinase 1 expression which induces cofilin dephosphorylation i.e. inhibition of neuritogenesis
  • increase intracellular Ca2+ in response to membrane depolarisation
52
Q

What do commissural axons in drosophila do?

A

cross the midline once due to Comm being switched on

53
Q

Where is Comm switched off?

A

in ipsilateral neurons and post-crossing commissural neurons

54
Q

What does Comm do and how?

A

regulate the sensitivity of axons to the midline repellent Slit by controlling the intracellular trafficking of Robo, the slit receptor

55
Q

What are the 4 major families of axonal instructive guidance cues and receptors?

A
  • netrin/UNC-5/DCC
  • slit/Robo
  • ephrin/Eph receptor
  • semaphorin/semaphorin receptors
56
Q

What activates and inactivates Rho GTPases respectively?

A
  • GEF (guanine nucleotide exchange factor) activates
  • GAP (GTPase activating protein) inactivates
57
Q

Give an example of guidance cue signalling

A

growth cone collapse caused by semaphorins

58
Q

What does combinatorial assembly of semaphoric receptors do?

A

increase the diversity of ligands to which a family of guidance receptors can respond

59
Q

What can addition of UNC-5 subunits to a DCC receptor complex do?

A

convert the guidance response from attractive to repulsive

Neuro Development and Disease (9 decks)

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