Neuronal Development, Survival & Differentiation Flashcards
What is the ratio of neurons to glia cells?
10 % = neurons
90% = gliaCEl
Origin of nerve cells
- Neurons & glia = neuroepithelium, ectoderm
- Microglia = yolk sac
microglia are derived from embryonic mesoderm, which gives rise to cells of the blood and immune system.
Neural tube becomes…
Neural progenitors (single layer, pseudostratified columnar)
What is the process of cell division in progenitor expansion phase (phase 1)?
Symmetrical cell division, interkinetic nuclear migration
The 1st generation of neural tube zones
- Preplate PP - 1st gen neurons = pial surface
- Intermediate zone IZ - axons
- Ventricular zone VZ - proliferative zone, radial glial cell body
How does migration on radial glia work?
The migrating neuron has CDK, neuregulin, NMDA-R1, integrin
The radial glia has integrin, laminin, fibronectin, NGCAM
Non-radial migration
Occurs horizontally, at the same time as radial migration
1. DISTRIBUTION OF INHIBITORY GABAergic neurons
2. Formation of brainstem nucleu
What layers does the preplate form?
- Marginal zone
- Cortical plate
- Subplate (will eventually disappear)
The marginal zone becomes which cortical layer?
Cortical layer I, the first layer
The cortical plate develops …
Inside out, from cortical layer VI (closer to the ventricle) to cortical layer II (closer to the marginal zone or cortical layer 1)
Which zone becomes white matter?
Intermediate zone
The ventricular zone becomes
The subventricular zone.
The embryonic layer: ventricular zone goes away.
Sematophorin 3A
Axon goes down (away from higher concentration of semaphorin = long-range chemorepellent)
Dendrite goes up (pial surface)
This is a long-range cue for growth of axon.
Growth cone
Filopodia = feet = actin bundles
Lamillopodia = notch between feet = actin-myosin meshwork
Growth according to chemical signals.
Cadherins
Diffuse in ECM, contact attraction for the growth cone = the roadway
Ephrin
Contact repulsion, roadway guard rails
Netrins
Chemoattraction for growth cone, long-range cues
Mature neurons can be seen in LM due to
Nissl substance
Lipofuscin is found in
DRG
Sympathetic ganglion
Pyramidal neurons
Neuromelanin
Substantia nigra (dopamine)
Kinesin
Anterograde transport
Slow axonal transport for…
Cytoskeletal properties: neurofilaments, microtubules, axonal matrix
Fast axonal transport
Membrane bound organelles, vesicles, neurotransmitters, neuropeptides
Retrograde transport
Motor: Dynein,
Neurotrophic factors (NGF), rabies virus
neuron reaction to injury
Chromatolysis
Wallerian degeneration
Neuron cell body reaction to injury
“Chromatolysis” = Chromatolysis is a reactive change that occurs in the cell body of damaged neurons, involving the dispersal and redistribution of Nissl substance (rough endoplasmic reticulum and polyribosomes) in order to meet an increased demand for protein synthesis such as is required to regenerate axons.
Nuclear eccentricity
Cell swelling
Dispersed Nissl substance
Wallerian degeneration
Wallerian (orthograde) degeneration is axonal degeneration occurring distal to the site of injury.
Wallerian degeneration is an active process of retrograde degeneration of the distal end of an axon that is a result of a nerve lesion. It occurs between 7 to 21 days after the lesion occurs. After the 21st day, acute nerve degeneration will show on the electromyograph
Process of nerve regeneration
- Degeneration
- Phagocytosis by macrophages and Schwann cells
- Schwann proliferation
- regeneration of axon along endoneurial tube
Neutrophin family receptors…
Tyrosine kinase
NGF Nerve growth factor
Stimulates cholinergic forebrain neurons. May help in Alzheimer’s patients.
The NGF gene provides instructions for making a protein called nerve growth factor beta (NGFβ). This protein is important in the development and survival of nerve cells (neurons), especially those that transmit pain, temperature, and touch sensations (sensory neurons).
BDNF, NT-3, NT-4
Neutrophins
NGF pathway
- Ras-MAP
- Phospholipase C
- Phosphatidylinositol-3-kinase (PI3K)
This happens by retrograde transport from axon, stimualting growth survival and neuronal differentiation.
Where are adult neural stem cells found?
- Subgranular zone of the dentate gyrus
- SVZ of lateral ventricles
Symmetrical vs asymmetrical cell division
Symmetrical is for growing the NP pool.
Asymmetrical is for dividing into radial glia and neurons.
What came first: neurons or glia?
Neurogenesis occurs first, then gliogenesis.
How do glia cells develop?
Multipotent stem cells become glial progenitors, which start differentiating into astrocytes via Notch activation.
The astrocytes release PDFG, NT-3 which causes oligodendrocyte progenitor cell proliferation. After a while, cell cycle inhibitor p27Kip1 accumulates and tells them to stop dividing and start maturing.
How do neural crest cells differentiate?
Proneural genes are activated by AMP from aorta, becoming SA progenitor.
SA progenitor becomes sympathetic neurons if activated by bFGF, but will become chromaffin cells if the are activated by glucocorticoids in adrenal gland.
BMP2
Crest cells become neurons
Neuregulin/GGF2
Crest cells become glia
Macroglia make up … of glia cells
80%
What is the most abundant cell in the CNS?
Astrocytes
Neuroglia express …, intermediate filaments.
GFAP = glia fibrillary acidic protein
Can be used in immunostain to find astrocytomas.
Which glia produces neurotrophic factors?
Astrocytes
Which glia induces BBB?
Astrocytes
Schwann cell origin
Neural crest, same as skin melanocytes
Interferon beta
Slow MS progression
Improves integrity of BBB
Overactivity of which glia cell may produce ALS, Parkinson, etc?
Microglia
Ependymal cells
Ciliated cuboidal epithelial cells
They line the ventricles and central canal.
Gap junctions.
Lens and cornea developed from ….
Ectoderm
Anterior pituitary developed from …
Ectoderm
Retina developed from …
Neural tube
The notochord develops from …
Mesoderm
When does the neural tissue know that it will become NS?
Gastrula phase
Does the involuting mesoderm responsible for neural tube induction become a part of the NS?
No. It disintegrates.
Noggin
the first neural inducer identified
Noggin was capable of specifically inducing neural genes, without inducing mesodermal genes.
Works by disinhibiting neuron formation.
Follistatin, Chordin
Inhibits TGF-beta along with Noggin. Works by disinhibiting neuron formation.
What is the chemical that adjacent cells use to inhibit neuron formation?
BMP induces epidermal cell lines by activating Smad second messenger.
What gene is responsible for neural induction?
bHLH genes
basic Helix-Loop-Helix transcription factors
Remark: in chicks, the ligand responsible for activating these genes is FGF
