Development of cortex

Development of cortex

1. From tube to laminae...

   • How does the one-cell thick neural tube turn into the multiple layered cortices of the cerebrum and cerebellum?
     • Neural tube initially one cell thick
       • Cells divide by nuclear translocation
         • Marginal zone relatively cell- free
         • Division ↑↑ after neuropores close
   • What happens if it doesn't?
     • Developmental abnormalities
       • Lissencephaly
       • Smooth brain
         • Agyria
     • Migration abnormalities

2. Cerebral cortex

   • Post-mitotic cells move from ventricular zone to form preplate
     • Cortical plate
       • Splits PP
       • Forms many layers of adult cotex
   • Cajal-Retzius cells in marginal zone
     • 1st post-mitotic cells
       • Disappear or change phenotype later
     • Cajal-retzius cells secrete reelin
       • 3460 amino acids, ECM-like
       • Reeler mice
         • Preplate forms but cortical layers malformed
         • Parallels to lissencephaly
       • Stops migrating cells?
         • Unclear role
         • Repellent / stop signal?
     • CR development regulated by Foxg1
       • Foxg1 -/- has extra CR cells
   • Subplate

3. Inside out development

   • Using 3H – thymidine to find cell birthdays
   • Cortical layers
     • Subventricular zone appears
       • Localised (Sanes) or widespread
       • Also a germinal layer
     • White matter tracts and other layers form

4. Guiding migration

   • Cell movement is often associated with radial glia
     • Radial glia have astrocyte markers
     • Most disappear after development
       • Except bergmann glia
         • What are they?
     • Are stem cells
   • But some is tangential (e.g. cortical interneurons)

5. Cerebellum

   • Forms at the roof of the IVth ventricle
     • Cortical region
       • Cortical layers
     • Central nuclei
       • Deep cerebellar
     • Roof of IVth very thin
       • VZ is close to surface
       • Rhombic lip cells (germinal trigone) at the superior and inferior edges of the medullary velum
         • Whut?
         • Superior rhombic lip cells form the external germinal layer
   • Forms at boundary of the mid and hindbrains
   • Development
     • Superior rhombic lip cells form the external germinal layer
       • VZ produces all other cell types
       • Inferior lip produces pontine nuclei and inferior olive
     • The EGL produces granule cells (neurons)
       • Granule cells migrate inwardly
         • Cerebellar mass increases as granule cells ↑↑
           • Folds appear

6. Control of development

   • Production of rhombic lip cells is regulated by MATH-1 (transcription factor)
     • No MATH-1 no foliation, no IGL, no pontine nuclei
     • Pontocerebellar hypoplasia
       • Find a picture and research it a bit
   • Sonic HH released from Purkinje cells stimulates mitosis in EGL
   • Reeler mice - disordered layers
     • Reelin from EGL
     • Other factors

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