Axon Guidance

Axon Guidance

1. Stages of Pathway Formation

   • Pathway selection
     • Eg. Where to go at optic chiasm
   • Target selection
     • Eg. Which thalamic nucleus to innervate
   • Address selection
     • Eg. Select correct LGN layer

2. Chemoaffinity

   • Chemical markers on growing axons matched with complimentary chemical markers of their targets

3. Chemorepellents (eg. slit) and chemoattractants (eg. netrin)

   • Netrin secreted in ventral midline of spinal cord
   • Gradient of netrin attracts axons of dorsal horn
     • Neurons cross midline and form spinothalamic tract
   • Once axons cross midline, faced with slit
     • Expresses robo protein
   • Growth cones attracted to midline express little robo
     • Repulsed by slit
   • Once crossed midline, signal up-regulates robo
     • Axons attracted to slit
   • Axons grow away from midline

4. Retinal axons growth into optic tectum of frog

   • Gradient of Ephrin A2 and A5 in tectum (high in posterior
     • Neurons from nasal retina not repelled by either anterior or posterior tectum
     • Neurons from temporal retina repelled from posterior tectum
       • Eph A2 and A5 from tectum repells Eph A4, A5 and A3 in retina
   • Gradient of Eph A4, A5 and A3 in retina (high in temporal)
   • Eph B1 gradient along medio-ventral axis of tectum that repels EphB retino-ganglion cells to lateral and medium tectum

5. Guidance cues

   • Non-diffusable
     • ECM molecules (laminins, fibronectins, collagens)
     • Calcium-independent cell-adhesion molecules
     • Calcium-dependent cell adhesion molecules (cadherins)
     • Ephrins chemorepell through Eph receptors
   • Diffusable
     • Netrins = cAMP-dependent chemoattractants or chemorepellents
       • Netrin receptors (eg. DCC)
     • Semaphorins chemorepell
       • Neutropilins and plexins
     • Slit proteins chemorepell
       • Robo receptors

Images and files in the map