Embryology II-IV Flashcards
1
Q
Location of neurogenesis
A
- ventricular zones = layers closes to the ventricles @ brain/central canal @ spinal cord
2
Q
General process of neurogenesis
A
- neurectoderm ==> neural tube ==> begining of neurogenesis (Day 22)
- most neurogenesis is embryonic, but some postnatal
- precursors @ different regions in CNS behave differently ==> patterning events
3
Q
Neurogenesis definition
A
- =process of generating neural cells
4
Q
Nucleaur positioning during cell cycle of neuronal precursors
A
- dividing cells have processes that attach medially to the ventricular surface & laterally to external surface
- position of nucleus changes as cell continues through cell cycle
- @ S = most superficial
- @ M = most deep
5
Q
Common methods used to study neurogenesis
A
- label dividing cells w/detectable DNA precursors
- cells take up labled precursors during S phase
- label allows tracking of cells and progeny
6
Q
“Cell birthdate” definition
A
- =time a cell finishes l_ast round of DNA synthesis_ ==> divides ==> exits cell cycle from M phase
- after cell birthdate ==> neuronal differentiation begins
- cells with similar birthdays end up in the same layer ==> time when a neuron is born has a big impact on its fate
7
Q
Secondary zones of neurogenesis definition/examples
A
- =brain regions that undergo postnatal neurogenesis
- cerebellum: granule neurons
- external granule layer
- oflactory neurons
- subventricular zone ==> olfactory bulb neurons
- hippocampal neurons
- dentate gyrus
8
Q
Formation of cerebellar granule neurons
A
- precursors @ rim of 4th ventricle ==> migrate while still dividing ==>
- new neurogenic region = “external granule layer”
- granule cell progenitors proliferate ==> “born” ==> migrate to cerebellum
9
Q
Shared characteristics of cells in secondary zones of neurogenesis
A
- arise in ventricular zone
- migrate before exiting mitotic cycle to new, non-ventricular location
- proliferate postnatally @ non-ventricular location
10
Q
Adult neurogenesis
A
- neurogenesis in adults @:
- dentate gyrus
- subventricular zone
- also cell death occuring ==> no total increase in neurons
11
Q
Perpendiciular vs. parallel progenitor cell division
A
- perpendicular = plane of division is perpendicular to ventricular surface
- both daughter cells remain attached to ventricular surface
- majority of these cells remain in cell cycle
- parallel = plane of division is parallel to ventricular surface
- one daughter cell attached to ventricular surface and one is not
- “assymetric division”
12
Q
Characteristics of assymetric division
A
- parallel division ==> one unattached daughter cell
- unattached cell ==> begins differentiation
- plane of cleavage may impact inheritance of various factors (e.g. proteins, mRNAs)
13
Q
Preplate definition and division
A
- cerebral cortex region formed by first postmitotic, migrating neurons
- divides into (from superficial ==> deep): marginal zone, cortical plate, the subplate, intermediate zone, and deep ventricular zone
14
Q
Subplate characteristics
A
- formed from division of preplate
- neurons @ SP = earliest born & are “poineers” of circuit formation
- many neurons die early after completing role
- ~transient neuronal population
15
Q
Glial role in neuronal migration
A
- radial glia extend from ventricle to surface
- neurons use glia as “guides” during migration
- wave of neurogenesis finishes ==> neurons migrate into cortical plate via radial glia
16
Q
Pattern of neuronal migration into cerebral cortex
A
- “inside-out” pattern
- neurons born later migrate past first-born neurons
- first-born neurons = closest to ventricular surface
- later-born = closest to pial surface
17
Q
Stages of neuronal migration @ cerebral cortex
A
- onset of migration
- starting of migration
- involves modulation of actin cytoskeleton in order to initiate
- ongoing migration
- continued migration along radial glia past earlier-born neurons w/recognition of distinct layers
- migration stop
- recognition of appropriate layer and disengagement from radial glia
- Reelin proposed as involved
18
Q
FLNA gene characteristics
A
- FLNA = filaminA ==> actin-binding crosslinking protein
- defects in FLNA lead to inability to initiate neuronal migration ==> periventricular heterotopia
19
Q
LIS1 gene characteristics
A
- LIS1 believed to produce a protein that regulate microtubular cytoskeleton fxn associated w/nuclear movement
- defect impacts ongoing neuronal migration and leads to Type I lissencephaly
- neurons begin migration but do not make it to cortical plate
20
Q
DCX gene characteristics
A
- Neurons express DCX as they migrate ==> believe to regulate microtubular cytoskeleton
- defect impacts ongoing neuronal migration ==> double cortex syndrome
21
Q
Reeler gene characteristics & associated genes
A
- [in mice] reeler encodes reelin protein = large extracellular protein
- expressed by Cajal-Retzius cells @ marginal zone and preplate
- defect leads to problems stopping neuronal migration ==> inverted inside-out pattern
- Vldlr & Apoer2 = cerebbelar & cerebral reelin receptors
- Dab1 = intracell protein in reelin signal transduction
22
Q
Retinal pattern of neural migration
A
- reversed compared to cerebral cortex
- follows an “outside-in” order
- ganglion cells are born first and photoreceptors are born last
23
Q
Radial migration definition + cell types
A
- = migration along radial glia
- accounts for most of migration
- cells: many of cerebral cortex undergo radial migration
- Glutamate-containing neurons (pyramidal cells)
24
Q
Tangential migration definition + cell types
A
- tangential migration ==> cells dispersed through developing tissue
- cells: inhibitory GABA-containng cells in cerebral cortex
- migrate from lateral/medial ganglionic eminences
25
Q
Chain migration definition + cell types
A
- = neuronal precursors move as chains along the rostral migratory stream pathway
- neurons from the subventricular zone near lateral ventricle ==> olfactory bulb
26
Q
Neural crest orgin and future structures
A
- neural crest = mass of cells on top of dorsal tube between the neuroectoderm and epidermis
- neural crest cells ==> peripheral nervous system + variety of other cell types
27
Q
Neural crest migration vs. Radial migration
A
- neural crest cells migrate fast, w/out guiding cells
- express integrins = receptors for laminin and fibronectin @ ECM
- fate influenced by rostro-caudal position prior to migration
- migratory patterns:
- dorsal stream => pigment cells
- ventral stream => sensory, autonomic, and enteric ganglia
28
Q
Apoptosis vs. Necrosis
A
- necrosis: response to extreme physio conditions ==> death of cells via loss of membrane integrity
- associated w/trauma or external injury
- apoptosis: occurs under normal physio conditions and cell actively participates in own demise
- involved in development
29
Q
Timing & purpose of cell death w/in nervous system development
A
- purpose: pattern formation, brian morphogenesis, removal of unnec. neurons, etc.
- timing: coincident w/establishment of connection by a particular neuronal population
30
Q
Neurotrophic hypothesis
A
- targets provide limiting amounts of nutrient (trophic factor) taken up by input nerve terminals
- determines how many neurons die/survive at post-synaptic organs
31
Q
Neurotrophic factors/neurotrophis definition
A
- molecules released by targets that promote cell survival
- inhibit apoptosis
- neurotrophins = family of related proteins
- NGF (nerve growth factor)
- BDNF (brain-derived neurotrophic)
- NT-3 (neurotrophin-3)
- NT-4/5
- also regulate neuronal development and function
32
Q
Examples of long-range (diffusible) axon guidance molecules
A
- attractive
- netrins
- repulsive
- semaphorins, netrins
33
Q
Examples of short-range (contact-dependent) axon guidance molecules
A
- attractive
- cell surface: cadherins, CAMs
- ECM: collagen, laminin, fibronectin, proteoglycans
- repulsive
- cell surface: semaphorins, ephrins
- ECM: tenascin
34
Q
Factors that impact axonal regeneration
A
- ability of axons to grow
- CNS axons can regenerate long distance
- growth-promoting molecules
- glial environment (e.g. Schwann cell) may produce NGF/other trophic factors
- fibroblast growth factor (FGF)
- molecules/receptors that inhibit growth
- CNS myelin expresses molecule that prevents axonal regeneration (Nogo)
35
Q
Synapse elimination definition + timing/location
A
- initial excess of neurons contacting cells ==> eliminate synapses via a competitive process = selective synapse elimination
- __e.g. muscles during embryonic/early postnatal life = polyneuronal innervation ==> single neuron innervates
- also occurs @ CNS; e.g. cerebellum @ purkinje cells; visual & auditory systems
36
Q
Mechanism of synaptic elimination
A
- electrical activity helps facilitate synapse elimination
- correllated firing of pre and post-synaptic = synpase stabilization
- vs. uncorrelated promotes elimination
- once activated, post-synaptic cell often releases neurotrophin/growth factor
37
Q
Postnatal changes in brain morphology
A
- @ birth: low density of neural connections
- ==> increase in size of soma and interconnections between neurons
38
Q
ASD and postnatal brain morphology
A
- ASD brains ==> abnormally high increases in size (especially in white matter areas)
- smaller neuronal cell bodies and fewer branching of dendrites
39
Q
Down’s Syndrome and postnatal brain morphology
A
- dendritic abnormalities = abnormally thin and short
40
Q
Timing of myelination development
A
- begins during embryonic stages
- present first @ periphery
- @ CNS:
- myelination @ spinal cord near the end of the first trimester
- myelination @ brain by end of third trimester
- myelination @ some higher fxn cortical tracts occurs after birth
41
Q
Regulation of GABA receptors during development
A
- GABA receptors = several types of subunits
- some dominate during embryonic stages and some during adulthood
- GABA receptors = inhibitory @ adult, but = excitatory in utero
- excess intracell Cl- ==> ECl = depolarizing
