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
Chain migration definition + cell types
* = neuronal precursors move as chains along the rostral migratory stream pathway
* neurons from the subventricular zone near lateral ventricle ==\> olfactory bulb
26
Neural crest orgin and future structures
* 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
Neural crest migration vs. Radial migration
* 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
Apoptosis vs. Necrosis
* 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
Timing & purpose of cell death w/in nervous system development
* purpose: pattern formation, brian morphogenesis, removal of unnec. neurons, etc.
* timing: coincident w/establishment of connection by a particular neuronal population
30
Neurotrophic hypothesis
* 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
Neurotrophic factors/neurotrophis definition
* 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
Examples of long-range (diffusible) axon guidance molecules
* attractive
* netrins
* repulsive
* semaphorins, netrins
33
Examples of short-range (contact-dependent) axon guidance molecules
* attractive
* cell surface: cadherins, CAMs
* ECM: collagen, laminin, fibronectin, proteoglycans
* repulsive
* cell surface: semaphorins, ephrins
* ECM: tenascin
34
Factors that impact axonal regeneration
* 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
Synapse elimination definition + timing/location
* 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
Mechanism of synaptic elimination
* 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
Postnatal changes in brain morphology
* @ birth: low density of neural connections
* ==\> increase in size of soma and interconnections between neurons
38
ASD and postnatal brain morphology
* ASD brains ==\> abnormally high increases in size (especially in white matter areas)
* smaller neuronal cell bodies and fewer branching of dendrites
39
Down's Syndrome and postnatal brain morphology
* dendritic abnormalities = abnormally thin and short
40
Timing of myelination development
* 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
Regulation of GABA receptors during development
* 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
