Ventralisation of neural tube

Ventralisation of neural tube

1. Neurulation

   • Notochord
     • Below neural tube
     • Forms as neural tube and plate are forming
   • Neural tube 'pinches off' from overlying surface ectoderm
   • Medio-lateral axis transformed > Dorso-ventral

2. Notochord

   • Bilateral symmetry around midline
     • Do notochord and floor plate secrete organising signal?
       • Test
         • Graft donor notochord/floor plate to ectopic position in host
           • Ectopic floor plate neurons induced?
             • Yes!
               • Notochord is a source of a secreted factor that induces floor plate and motor neurons
                 • What is the factor?
                   • Shh
   • Forms as neural tube and plate are forming

3. Hedgehog/Shh

   • Conserved in vertebrates and invertebrates
     • Vertebrate homolog Shh
     • Shh signalling pathway: all worked out from the hh pathway in Drosophila
   • Acts as a morphogen
     • Much of outcome involves de-repression
       • Class 1 and 2 Transcription factors
         • Class 1
         • Class 2
   • Patterns early progenitor cells
     • Transcription factors expressed in response to gradient
   • Shh soaked bead
     • Ectopic floor plate
     • Ectopic ventral neurons
       • E.g. Motor neurons
   • Shh mRNA expressed in notochord then floor plate
     • Shh protein detected more widely
       • Appears in gradient
       • Cartesian grid
         • Intersects with A-P domain
   • Signalling pathway

4. Directed differentiation of es cells to neuronal fates

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