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Neuro_Week1 > 14- Embryo II > Flashcards

14- Embryo II Flashcards

1
Q

Primary neurogenesis

Where does it occur?

A

in ventricular zones

layers closest to ventricles in brain and central canal in spinal cord

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2
Q

Primary neurogenesis

When does it occur?

A

Occurs before birth

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3
Q

Secondary neurogenesis

When does it occur

A

post-natal

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4
Q

Secondary neurogenesis

Where does it occur?

A

cells in cell cycle migrate to new areas then continue prolif

3 main areas

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5
Q

Secondary neurogenesis

what are the 3 main areas

A

1) external granule layer –> cerebellum from cells near rim of 4th ventricle

2) subventricular zone –> olfactory bulb
- arise from cells located in anterolat wall of lateral ventricle
- not migrate very far compared to EGL layer

3) Dentate gyrus –> hippocampus

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6
Q

Changes in nuclear position during cell cycle of neuronal precursors

Mitosis occurs on __

DNA synth occur on __

A

Nucleus of prolif neurons move btwn ventricle side of ventricular zone to pia side and back

Mitosis occurs on ventricular surface
DNA synth occur on pia surface

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7
Q

Methods to study neurogenesis

A

labeling diving cells with detectable DNA precursors

most common = 3H-Thy and bromodeoxyuridine (BrdU- red stain)

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8
Q

describe actual procedure of methods

A

1) cell take up label in S phase
2) progenty tracked by label

3) see in real time or fixation/staining
used in vivo (mice)

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9
Q

What does a neurons’ birthdate mean?

A

time it undergoes its last round of DNA syntheiss (S phase)

after birthdate, a cell divides and makes decision to exit cell cycle from M phase

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10
Q

Does a neuron’s birthdate influence its differentiation?

A

only post-mitotic cells differentiate
(YES) A neuron’s birthdate influences its differenitation in that it cannot differenitate until it is born (aka leaves cell cycle)

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11
Q

What is known about neurogenesis in adult brain?

2 main areas where this occurs?

A

neurogenesis occurs in adult brain mostly in

dentate gyrus –> give rise to hippocampus
subventricular zone –> give rise to olfactory bulb

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12
Q

How does the # of neurons change during development

A

lots of cell death so little to no incr in #of neurons

neurons born post-natally more prone to cell death

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13
Q

Key questions for future research

A
  • why post-natal cells less viable?
  • figure out whether neuronal progenitors from these areas are able to populate other niches in brain
  • how to encourage progenitors or stem cells to properly differnitate and establish communication/circuit with other neurons
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14
Q

When a progenitor cell in ventricular zone divides, plane of cleavage can be either __ or ___ to the ventricular surface

A

parallel or perpendicular to ventricular surface

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15
Q

plane of cleavage perpendicular to cell divsion leads to what?

A

symmetric cell division

  • -> equal distrib of cyto proteins, mRNAs…
  • -> both daughter cells remain attached to ventricular surface
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16
Q

plane of cleavage parallel to ventricular surface leads to what?

A

asymmetric cell divsion

  • -> unequal distrub of cyto proteins, mRNAs
  • -> one daughter cell stay attach to ventricular surface - stays in cell cycle
  • -> one daughter cell no longer attach to ventricular surface (now a post-mitotic neuron and goes on to migrate and differenitate)
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17
Q

functions of prospero, numb, and miranda genes?

A

encode asymmetrically localized factors + role in cell fate deicsion

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18
Q

factors/mechanisms that determine when a cell stops dividing and begins differentiating

if plane of division for symm

if plane of division for asymm division

A

1) Factors (prospero, numb, etc.) that with sufficient quantitity induce cell to stop dividng, start differentiating
2) if plane of cell division is right for symmetric division, factors divide evenly and don’t reach threshold for diff
3) but if plane of division is for asymm division, factors cluster on external side (facing pia) so daughter cells that form without contact to ventricular wall can exit cycle and differentiate

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19
Q

Whaat is cerebral cortex arise from?

Layers of developing cortex

A

cerebral cortex comes from cortical plate

pia mater
basement membrane = laminin
marginal zone (cajal-retzius cells) = reelin
cortical plate
subplate cells 
intermediate zone
ventricular zone
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20
Q

Cells of cerebral cortex migrate in ___ pattern

what does that mean?

A

inside-out pattern

cells migrate from ventricle surface to cortical plate

first born cells found at bottom edge of cortical plate
later cells migrate past first born

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21
Q

compare retina development with cerebral cortex development

A

cortex = inside out

retina = outside in

ganglion cells born first and found furthest from VZ
photoreceptor sform last and closest to VZ

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22
Q

How is the preplate formed?

A

after leaving mitotic cycle cells leave ventricles and migrate to form preplate

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23
Q

preplate further divides to form what four zones

A

1) subplate = transient cell population “pioneering role” in circuits
2) intermediate zone = neuronal + glial cell processes
3) cortical plate = neurons of cerebral cortex
4) marginal zone = adj to pia with Cajal-Retzius cells expressing reelin

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24
Q

What role do radial glia play in neuronal migration?

A

extend from ventricle to pial surface

radial glia = guide or scaffold for cells as migrate from VZ to cortex layers

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25
Q

3 stages of neuronal migration

A

onset
continuation
stopping

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26
Q

describe onset of migration

what gene codes from actin-binding protein
what do mutations in gene cause?

A

1) cells get on radial glia
2) onset = perturbations to actin crosslinking coded by filamin A (FLNA)
3) mutations in FLNA = periventricular heterotopia (PH) = cells can’t leave the ventricle zone

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27
Q

describe continuation of migration

genes involved

A

1) Ability of cells to continue migrating along glia to final destination governed by microtubule function of cell
2) LISI and DCX = colocalize with MT and regul MT cytoskeleton

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28
Q

Mutations in LISI cause ___

Mutations in DCX cause ___

A

1) type 1 lissencephaly

2) double cortex syndrome

29
Q

describe stopping migration

1) protein involved
2) receptors on migrating cells
3) additional gene involved?

A

1) Reelin (coded by reeler gene) = large extracellular protein expressed by Cajal-Retzius cells in marginal zone
2) VIdIr and Apoer2 receptors on cells bind reelin = stop migrating
3) Dab1 = transduces reelin-receptor binding signal into migration termination

30
Q

Reelin involved in __

A

1) bind recepotrs on migrating cells = stop migrating

2) development of cerebellum

31
Q

defects in reelin lead to __

A

lissencephaly with cerebellar hypoplasia (LCH)

32
Q

Gene-gene product during onset of migration step

disorder assoc?

A

FLNA-actin binding crosslinking protein

disorder =periventricular heterotopia

33
Q

gene-gene product during continuation step

A

LISI-protein for regulation of MT function
mutation = Type 1 lissencephaly

DCX-protein fo rregul of MT function
mutation = “double cortex” syndrome = subcortical band of heterotropic neurons

34
Q

gene-gene product during stopping step

A

Reeler-large extracellular protein = Reelin

Vldr = receptor for Reelin in cerebellum

Apoer2-receptor = for reelin in cerebral cortex

Dab1-intracell protein for transducing reelin signal

Lissencephaly with cerebellar hypoplasia

35
Q 
Define radial migration
What class of neurons undergoes this type?
A

Cells move out from VZ along radial glia that project to surface of neural tube

cerebral cortex and glutamate-containing neurons

36
Q 
Define tangential migration
What class of neurons undergoes this type
A

cells migrate tangentially from ventricles

GABA-contianing cells

37
Q 
Define chain migration
What class of neurons undergoes this type
A

neurons in chains thru rostral migratory stream (from SVZ to olfactory bulb)
neurons of olfactory bulbs

38
Q

neural crests arise from?

made of?

fate of neural crest cells determiend by?

A

arise from edge of neural folds btwn neuroectoderm and overlying epidermis

made of ectoderm

determined by position of rostro-caudal axis

39
Q

neural crest cells give rise to ___

A

sensory ganglia,
sympathetic neuroblasts, Schwann cells,
pigment cells,
odontoblasts, meninges mesenchyme of the pharyngeal arches

40
Q

Describe trunk path of neural crests

what does each sub-path give rise to?

A

gives rise to two streams of migrating neural crest = ventral and dorsal stream

dorsal = pigment cells

ventral = under dorsal dermatomyotomes –> sensory, autonomic, and enteric ganglia

41
Q

contrast migration of neural crest cells to radial migration in cortex

A

neural crest cells = migrate quick without guides

radial migration = slower and requires guide cells (radial glia)

42
Q

migration of neural crest cells under the influence of ___

A

proteins in environment they are migrating in

neural crest cells express integrin receptors that bind “permissive components of ECM” for migration

also bind “non-permissive signals” –> inhibit migration

==> patterning of neural crest

43
Q

migration of neural crest terminated with ___

A

upregulation of adhesion molec in neural crest cells (cadherins)

44
Q

radial migration patterning guided by __

migration terminated by ___

A

radial glia and regulation of cells’ cytoskeleton

migration terminated by receptors binding reelin

45
Q

compare and contrast apoptosis with necrosis

A

necrosis = death of cells d/t loss of membrane integrity

  • mitochondria and ER swell
  • release intracell contents and expose neighboring cells to toxic substance

apoptosis = programmed cell death requiring cell to make new mRNA and proteins assoc with apoptotic path

  • recruits phagocytes to remove cells
  • prevents neighboring cells from exposure to intracell contents
46
Q

necrosis most commonly assoc with

apoptosis most commonly assoc with what

A

external injury, trauma, or extreme physiological changes

developing NS

47
Q

when does cell death occur in nervous system?

A

during establishment of connection by particular neuron population

neurons compete for limited neurotrophic survival factors at target sites

48
Q

what are neurotrophins

A

neurotrophic factors = survival factors @ synapse btwn target and developing neuron

neurons compete for these factors (NGF, BDNF, NT3, NT4/5)
and interact with receptors (TrkA, TrkB, TrkC)

49
Q

function of neurotrophins in neuronal development

A

each neurotrophin –> activates 1+ receptor
–> dimerization of Trk proteins and recruitment of signaling molec in cell

–> suppression of apoptosis in developing neurons

50
Q

NGF = most common receptor?

BDNF = most common receptor?

NT3 = most common receptor?

A

TrkA

TrkB

TrkC

51
Q

what is at tip of growing neuron?

Function?

A

growth cone –> constantly samples envrionment by extending filopodia

growth cone can then stop, turn, retract, or continue growing

52
Q

what are 2 classes of guidance signals for growth cones?

A

long-range chemotaxis

short range, local substrate cues

53
Q

long distance signals vs short range signals

A

long distance = diffusible and create attractive gradient (induce growth towards) or repulsive (induces growth away)

short range = bound to cell membrane of local or ECM and require direct cell-cell contact

54
Q

name of long range axon guidance attractive molec

name of short range axon guidance attractive molecs

A

long range = netrins

short range =

  • on cell surface (cadherins, CAMs)
  • on ECM (collagen, laminin, fibronectin, proteoglycans)
55
Q

name of long range guidance repulsive molec

name of short range axon guidance molecs

A

long range = semaphorins, netrins

short range =

  • on cell surface (semaphorins, ephrins)
  • on ECM = tenascin
56
Q

semaphorins can be long range or local depending on ___

A

tethered to membrane or if cleaved/secreted

57
Q

Factors that influence ability of axons to regenerate

A

1) ability of axons to grow (PNS regenerate; CNS can’t but still can grow)

2) presence of growth molec
(Schwann produce NGF for regen; FGF and neurotrophins in PNS help process;
CNS + glia don’t express growth factors)

3) presence of molec and receptors that inhib growth
(CNS myelin express Nogo= inhib molec that prevents axon regeneration)

58
Q

describe normal postnatal changes in brain morphology

@ birth density of neural connections

during 1st yr of life neuron changes?

A

at birth = density of neural connections low compared to child

during 1st yr, soma incr in size, # of dendrite incr, dendrite spine thicken

incr # of connections

59
Q

How does ASD affect normal development in neuronal morphology?

A

brain is normal or small at birth

during first few yrs, incr in brain size abnormally esp in white matter

soma small
dendrites branch less

due to abnorml brain circuitry

60
Q

How does Down syndrome affect neuronal morphology

A

spines of dendrites abnormally thin and short

61
Q

Where does beginning of myelination occurs?

when does CNS myelination occur?

when does CNS myelination reach brain?

A

begin in periphery of embryo

CNS myelination at end of 1st trimester in spinal cord

Reach brain by 3rd trimester

62
Q

when does myelination of cortical tracts begin?

when does myelination of corticospinal tract begin?

A

Myelination of cortical tracts in higher brain function occur post-natally

Myelination of corticospinal tract begins pre-natally but not extend past medulla in caudal direction until after birth

63
Q

structure of GABA receptors

A

oligomers –> more than 1 subunit

each has multiple isoforms

64
Q

2 ways that function of GABA receptors is developmentally regulated

A

different isoforms –> different properties to GABA for regulation of equilibrium potential for chloride

during embryonic development,, intracellular chloride is higher and E-Cl more depol –> GABA excitatory

65
Q

Define synapse elimination

A

selective removal of immature synapses formed b/c neuron initially has >1 target

66
Q

How does synapse elimination change # of synapses

A

of synapse incr

67
Q

Where does synapse elimination occur?

A

cNS and PNS

68
Q

What happens in PNS?

How does this lead to a change in muscle fiber innervation?

A

muscle fibers have >1 neuron innerv it

synapses strengthened by synch firing of pre- and post-synaptic cells

asynchronous firing –> elimination

after post-syn cell activ by synch firing –> release neurotropin to pre-synap cell

neurotropin –> structural change that strengthens some NMJs while others are weakened until each muscle fiber innerv by single motor neuron

69
Q

How are synapse stabilization occur in developing cerebellum?

A

1) many climbing fibers innerv single Purkinje cells

2) synapse elim occur by competition for target

Neuro_Week1 (26 decks)

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