Patterning the AP axis

Patterning the AP axis

1. Organiser

   • Molecules from organiser induce neural tissue
     • How do they induce neural tissue of different A-P types?
       • Activation transformation model

2. Activation-transformation model

   • If true - should be able to uncouple anterior and posterior development
     • Evidence
       • Early embryo
         • Complete secondary axis
       • Late gastrula stage
         • Only posterior neuraxis
   • Neural inducing molecules induce (and then maintain) anterior (forebrain) tissue
     • These molecules initially come from early organiser cells but are maintained only in the prechordal tissue once the organiser has differentiated
       • Other signals then transform some of this to a more posterior fate
         • Posteriorising signals are antagonised by prechordal tissue

3. Midbrain

   • Forms at junction of hindbrain and forebrain
     • Transplant hindbrain > forebrain
       • Induces ectopic midbrain
     • Specialised signalling boundry
       • Forebrain
         • OTX2
       • Hindbrain
         • GBX2
       • Isthmus
         • 'Organiser-type' region
         • Wnt1
         • FGF8
         • Both responsible for local proliferation and induction of adjacent tissue to new 'midbrain' (and more complex midbrain fates)

4. Hox genes

   • Rhombomeres
     • Particular nerves derive from discrete rhombomeres
       • Governed by expression of hox profile
   • Activated by particular threshold concentrations of posteriorising signals
   • DNA encodes DNA binding protein domain of 60 amino acids
     • Homeodomain
   • 'Homeobox containing'
   • Identified in drosophila
     • Vertebrate homologues
     • Specify A-P segment identity

5. Molecular basis

   • 1) Before gastrulation, cells in the organiser secrete BMP and Wnt inhibitors that induce neural tissue of anterior character
     • 2) After gastrulation, only bits of axial mesoderm that involuted first (pharyngeal endoderm - orange arrows and prechordal mesoderm - first green arrow continue to make these molecules)
       • 3) Cells in the forming posterior part of the embryo (last 3 arrows) now start to make posteriorising signals which all act to posteriorise induced anterior tissue
         • In a gradient
           • Highest concentrations posteriorly
         • In prospective forebrain BMP and Wnt inhibitors ensure no posteriorising signals function
           • Maintains some anterior neural tissue

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