14- Embryo II Flashcards
Primary neurogenesis
Where does it occur?
in ventricular zones
layers closest to ventricles in brain and central canal in spinal cord
Primary neurogenesis
When does it occur?
Occurs before birth
Secondary neurogenesis
When does it occur
post-natal
Secondary neurogenesis
Where does it occur?
cells in cell cycle migrate to new areas then continue prolif
3 main areas
Secondary neurogenesis
what are the 3 main areas
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
Changes in nuclear position during cell cycle of neuronal precursors
Mitosis occurs on __
DNA synth occur on __
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
Methods to study neurogenesis
labeling diving cells with detectable DNA precursors
most common = 3H-Thy and bromodeoxyuridine (BrdU- red stain)
describe actual procedure of methods
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)
What does a neurons’ birthdate mean?
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
Does a neuron’s birthdate influence its differentiation?
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)
What is known about neurogenesis in adult brain?
2 main areas where this occurs?
neurogenesis occurs in adult brain mostly in
dentate gyrus –> give rise to hippocampus
subventricular zone –> give rise to olfactory bulb
How does the # of neurons change during development
lots of cell death so little to no incr in #of neurons
neurons born post-natally more prone to cell death
Key questions for future research
- 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
When a progenitor cell in ventricular zone divides, plane of cleavage can be either __ or ___ to the ventricular surface
parallel or perpendicular to ventricular surface
plane of cleavage perpendicular to cell divsion leads to what?
symmetric cell division
- -> equal distrib of cyto proteins, mRNAs…
- -> both daughter cells remain attached to ventricular surface
plane of cleavage parallel to ventricular surface leads to what?
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)
functions of prospero, numb, and miranda genes?
encode asymmetrically localized factors + role in cell fate deicsion
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
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
Whaat is cerebral cortex arise from?
Layers of developing cortex
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
Cells of cerebral cortex migrate in ___ pattern
what does that mean?
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
compare retina development with cerebral cortex development
cortex = inside out
retina = outside in
ganglion cells born first and found furthest from VZ
photoreceptor sform last and closest to VZ
How is the preplate formed?
after leaving mitotic cycle cells leave ventricles and migrate to form preplate
preplate further divides to form what four zones
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
What role do radial glia play in neuronal migration?
extend from ventricle to pial surface
radial glia = guide or scaffold for cells as migrate from VZ to cortex layers
3 stages of neuronal migration
onset
continuation
stopping
describe onset of migration
what gene codes from actin-binding protein
what do mutations in gene cause?
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
describe continuation of migration
genes involved
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
Mutations in LISI cause ___
Mutations in DCX cause ___
1) type 1 lissencephaly
2) double cortex syndrome
describe stopping migration
1) protein involved
2) receptors on migrating cells
3) additional gene involved?
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
Reelin involved in __
1) bind recepotrs on migrating cells = stop migrating
2) development of cerebellum
defects in reelin lead to __
lissencephaly with cerebellar hypoplasia (LCH)
Gene-gene product during onset of migration step
disorder assoc?
FLNA-actin binding crosslinking protein
disorder =periventricular heterotopia
gene-gene product during continuation step
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
gene-gene product during stopping step
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
Define radial migration What class of neurons undergoes this type?
Cells move out from VZ along radial glia that project to surface of neural tube
cerebral cortex and glutamate-containing neurons
Define tangential migration What class of neurons undergoes this type
cells migrate tangentially from ventricles
GABA-contianing cells
Define chain migration What class of neurons undergoes this type
neurons in chains thru rostral migratory stream (from SVZ to olfactory bulb)
neurons of olfactory bulbs
neural crests arise from?
made of?
fate of neural crest cells determiend by?
arise from edge of neural folds btwn neuroectoderm and overlying epidermis
made of ectoderm
determined by position of rostro-caudal axis
neural crest cells give rise to ___
sensory ganglia,
sympathetic neuroblasts, Schwann cells,
pigment cells,
odontoblasts, meninges mesenchyme of the pharyngeal arches
Describe trunk path of neural crests
what does each sub-path give rise to?
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
contrast migration of neural crest cells to radial migration in cortex
neural crest cells = migrate quick without guides
radial migration = slower and requires guide cells (radial glia)
migration of neural crest cells under the influence of ___
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
migration of neural crest terminated with ___
upregulation of adhesion molec in neural crest cells (cadherins)
radial migration patterning guided by __
migration terminated by ___
radial glia and regulation of cells’ cytoskeleton
migration terminated by receptors binding reelin
compare and contrast apoptosis with necrosis
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
necrosis most commonly assoc with
apoptosis most commonly assoc with what
external injury, trauma, or extreme physiological changes
developing NS
when does cell death occur in nervous system?
during establishment of connection by particular neuron population
neurons compete for limited neurotrophic survival factors at target sites
what are neurotrophins
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)
function of neurotrophins in neuronal development
each neurotrophin –> activates 1+ receptor
–> dimerization of Trk proteins and recruitment of signaling molec in cell
–> suppression of apoptosis in developing neurons
NGF = most common receptor?
BDNF = most common receptor?
NT3 = most common receptor?
TrkA
TrkB
TrkC
what is at tip of growing neuron?
Function?
growth cone –> constantly samples envrionment by extending filopodia
growth cone can then stop, turn, retract, or continue growing
what are 2 classes of guidance signals for growth cones?
long-range chemotaxis
short range, local substrate cues
long distance signals vs short range signals
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
name of long range axon guidance attractive molec
name of short range axon guidance attractive molecs
long range = netrins
short range =
- on cell surface (cadherins, CAMs)
- on ECM (collagen, laminin, fibronectin, proteoglycans)
name of long range guidance repulsive molec
name of short range axon guidance molecs
long range = semaphorins, netrins
short range =
- on cell surface (semaphorins, ephrins)
- on ECM = tenascin
semaphorins can be long range or local depending on ___
tethered to membrane or if cleaved/secreted
Factors that influence ability of axons to regenerate
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)
describe normal postnatal changes in brain morphology
@ birth density of neural connections
during 1st yr of life neuron changes?
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
How does ASD affect normal development in neuronal morphology?
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
How does Down syndrome affect neuronal morphology
spines of dendrites abnormally thin and short
Where does beginning of myelination occurs?
when does CNS myelination occur?
when does CNS myelination reach brain?
begin in periphery of embryo
CNS myelination at end of 1st trimester in spinal cord
Reach brain by 3rd trimester
when does myelination of cortical tracts begin?
when does myelination of corticospinal tract begin?
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
structure of GABA receptors
oligomers –> more than 1 subunit
each has multiple isoforms
2 ways that function of GABA receptors is developmentally regulated
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
Define synapse elimination
selective removal of immature synapses formed b/c neuron initially has >1 target
How does synapse elimination change # of synapses
of synapse incr
Where does synapse elimination occur?
cNS and PNS
What happens in PNS?
How does this lead to a change in muscle fiber innervation?
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
How are synapse stabilization occur in developing cerebellum?
1) many climbing fibers innerv single Purkinje cells
2) synapse elim occur by competition for target
