lec 10. CNS migration Flashcards
radial migration part 1
neuroepithelia divide at he apical surface in radial glial cells which divide into radial glial and neuronal precursor which moves radially
radial migration part 2
newborn neurons accumulate in the mantle layer, the newest ones occupying the most superficial layer.
tangential migration
neurons migrate up (in spinal cord and brain) which is important for bringing in inhibitory interneurons from the subpallium to the cortex and other developing areas
lissencephaly
caused by a mutation in microtubules (TUBA1A, TUBB2B, LIS1, DLX) which causes a failure of radial migration, and the preplate fails to separate. and by mutations in reelin
reelin function
reelin is a large ECM protein expressed by cajal cells in the marginal zone that tells migrating cells when to stop
also expressed by granule neurons in the cerebellum
reelin mutant
- preplate fails to separate
- disruption to RELN causes disruption of purkinje cell layer and in humans causes cerebellar hypoplasia
- mutation in reelin receptor (VLDLR) leads to cortical and cerebellar disruptions
preplate
made up of cajal retzius cells and subplate neurons which are the earliest post-mitotic cells
cortical plate
consists of later migrating neurons and exists in between Cajal cells and subplate neurons, and is where the major layers of the cortex form
adult neural stem cells and where they are found
begin as radial glial cells which become astrocyte-like. they are found in the SVZ of the 4th ventricle and denate gyrus of the hippocampus
3 types of inhibitory interneurons and where they migrate
gaba-ergic in cortex
dopaminergic in olfactory bulb
cholinergic in striatum
rhombic lip cells
similar to neural crest cells (they are proliferative, their daughters are migratory)
anterior rhombic lip cells
tangentially migrate to form the External Germinal Layer of the cerebellum which differentiates into granule neurons (Shh from purkinje layer stimulates mitosis here)
posterior rhombic lip cells
tangentially migrate to the ventral hindbrain (pontine nuclei and inferior olive)
granule neuron progenitors
derived from the rhombic lip and proliferate in the basal surface. they migrate tangentially first and then migrate radially
AT0H1 and knockout effect
regulates production of rhombic lip. knockout causes no foliation, no pontine nucleus, and no Internal Granular Layer and human cerebellar hypoplasia