neurogenesis Flashcards
what is the ventricular zone?
band around the lumen of the neural tube
what is the early neural tube described as?
1 cell wide neuroepithelium
OR
pseudo-stratified epithelium
DEFINE: interkinetic migration
nuclei shuttling up and down the process of the radial glial cell
how do neuroepithelial cells divide to give rise to neuronal progenitors?
- early neuroepithelial cells divide into 2 identical daughter cells
- daughter cells change shape and become radial glia cells
- radial glia divide asymmetrically to give rise to 1 identical radial glia daughter and a 2nd daughter that will differentiate into a neuron
- 2nd daughter migrates away from ventricular zone using scaffold provided by its sister’s process and becomes a neurogenic progenitor
Proneural genes
provide the competence to become neural cells
e.g. achaete scute
DEFINE: lateral inhibition
a special kind of inhibition that makes initially similar cells become different from one another by the transmission of an inhibitory signal between a pair or cluster of cells to prevent cells receiving the signal from adopting a particular fate
Describe the processes underlying the role of notch signalling in neurogenesis
- initially cell 1 and cell 2 express same levels of achaete-scute, notch and delta
- a slight imbalance in notch signalling results in cell 2 receiving more delta than cell 1
- notch signalling pathway is activated in cell 2
- notch upregulates suppressor of hairless
- suppressor of hairless upregulates enhancer of split
- enhancer of split represses achaete-scute
- achaete-scute maintains delta so in cell 2, delta is not expressed
- cell 1 no longer receives delta
- notch signalling normally suppresses achaete scute so in cell 1, achaete scute is expressed at high levels.
cell 1 becomes a neuronal precursor
cell 2 remains as a radial glial cell
during M phase of mitosis, where are the nuclei located during interkinetic nuclear migration?
near the lumen of the neural tube OR apical surface OR ventricular surface
Microtubule associated proteins
LIS1
DCX
Lissenchephaly
- missing sulci and gyri
- mutation in α-tubulin, β-tubulin, LIS1 and DCX = microtubule function
- mutation in Reelin
- failure of neuronal precursors to migrate along radial glial process
where are Cajal-Retzius cells formed?
marginal zone
Reeler mouse mutant
mutation in reelin = large ECM protein found in Cajal-Retzius cells
failure of cajal-retizius cells and subplate neurons to seperate + cortical plate forms beneath them
where are the two major zones of adult stem cells located in the adult brain?
- subventricular zone
- dentate gyrus of hippocampus
where do inhibitory interneurons of the cortex, olfactory bulb and striatum migrate in from?
subpallium
the inhibitory interneurons that go into the cortex are…….
GABA-ergic
the inhibitory interneurons that go into the striatum are…….
cholinergic
what are some methods used to trace neuronal migration?
- lipophilic dyes (to trace cells)
- transplantation experiments between quail and chick
- inject viruses carrying GFP into rodents –> infects ventricular zone
- induce fluorescent protein in just a subset of cells (conditional prelox)
where is the cerebellum located?
roof of 4th ventricle above the medulla
what do anterior rhombic lip cells give rise to?
granule neuron precursors
what do posterior rhombic lip cells give rise to?
pontine nuclei
inferior olive
MATH-1
transcription factor expressed in proliferating external germinal layer cells
also expressed in the pons
development of the cerebellum
- external germinal layer cells form on the outside of the neural tube
- EGCs = highly proliferative. at the same time, EGCs start differentiating into granule cells.
- differentiating granular neuron cell body migrate tangentially into inner granular layer
- differentiated granule cells extend their axons (parallel fibres) outwards into the EGL and synapse onto Purkinje cell dendrites
- purkinje cells located in the purkinje cell layer and they secrete Shh = mitogen for granular neuron precursor
DISEASE: pontocerebellar hypoplasia
smaller pons and cerebellum
mutation in MATH-1
where does the cerebellum arise from?
anterior rhombic lip cells