Neuro_Unit 3_Lec2 Flashcards
Early Neurulation Time
Coincides with Gastrulation (~18 days)
Early Neurulation Purpose
Defines the midline of the embryo and induces the formation of the neural ectoderm.
BMP
Growth factors that push the ectoderm towards the epidermal state.
Noggin/ chordin/Follistatin
Factors produced by the notochord which inhibit the BMP signal causing the cells to choose the neural fate (can be seen as the default pathway)
BMP signaling
- ) BMP binds to serine kinase receptor
- ) Receptor activates SMAD
- ) SMAD mediates transcription
FGF
signaling likely preceeds BMP and it critical for neural induction
Neural Crest formation
As the neural tube closes the neural crest pinches off and the roof plate forms
Neural Crest differentiation
Neural Crest gives rise to:
- ) Cranial neural crest
- ) Trunk neural crest
- ) Vagal and Sacral neural crest
- ) Cardiac neural crest
Dorsal Ventral Patterning
Ventral secretes Shh
Dorsal secretes BMP
(RA and FGF also play a role)
Shh signaling
- ) Shh binds to Patched
- ) PTC stops inhibiting SMO
- ) SMO activates the Gli class of zinc finger transcription factors
- ) Gli induces transcription which leads to ventral (motor neuron) cell fates
Absence of Shh signaling (sheep example)
Sheep ate cyclopamine which inhibits Shh
-eye field does not seperate
- nose above eye
Also absence leads to cancers like medulloblastomas and basal cell carcinoma because Shh regulates polarity, cell differentiation and proliferation
Anterior/ Posterior Patterning leads to:
- ) Spinal Cord
- ) Rhimbencephalon (pons and medulla)
- ) Mesencephalon (midbrain)
- ) Prosencephalon (thalamus and retina, forebrain)
HOX genes in the posterior CNS patterning
Define segmental differences in the spinal cord, medulla and pons through the action of multiple HOX genes repressing and enhancing each other.
NOT involved in the brain
OTX2 knockout mice
completely missing forebrain
Ventricular Zone
Thin strip of cells surrounding the CSF- filled ventricles
-neural stem cells and progenitor cells divide and differentiate in this zone to give rise to all the cells in the CNS.
Neural Stem Cells
Give rise to all cell types in the nervous system and have unlimited self renewal
Progenitor Cell
Can make neurons or glia but not both. Some can self renew for a few generations.
Symmetric and Asymmetric cell divisions in CNS development
Early- symmetric- 1 NSC to 2 NSCs
Middle- Asymmetric- 1 NSC to 1 NSC and 1 Neural progenitor
Late- Symmetric- symmetric- 1 NSC to 2 Neural progenitors
low/ moderate levels of Notch stimulation by Delta
CONTACT DEPENDENT
1.) Intracellular domain of Notch is cleaved which activates bHLH genes
2.) bHLH activation upregulates Delta
for surrounding cells
3.) Notch gets hyper-activated in surrounding cells, which turns off those cell’s bHLH so they stay in their pluripotent NSC state.
Atrogliogenesis
opposite of what causes neurogenesis, happens later on to determine neuron vs glia cell
Atrogliogenesis needs high notch and low bHLH
Timing of Neurogenesis vs Gliogenesis
Nuerogenesis- majority generated by the middle of the second trimester
Gliogenesis- majority happens after birth (myelination also continues into your 20s)
Cortical development pattern (for projection neurons)
forms inside out due to radial migration
- earliest born are deeper closer to the ventricle
- later cells migrate along radial glia fiber to get where they are going
- leads to a column pattern when looking a cells derived from the same NSC. (form a functional unit in the cortex)
(discovered through thymidine labeling in monkey brains)
Reeler mutant
Problem with cortical development pattern. The later cells can’t get by the earlier cells, so the column develops upside down. Leads to Lissencephaly.
Interneuron migration
Tangential migration, come up and then dive back down.
