Axon guidance 2

Axon guidance 2

1. Morphogens

   • Gradients re-used to shape axon paths
     • Shh and BMPs
       • Cooperate with netrin to guide comissural axons

2. Growth cone

   • Dont turn, reorganise
     • When in contact with attractive cues
       • F-actin treadmilling slows
         • Accumulation
           • Stabilises filopodium
           • Drags microtubules into back of filopodium
   • Treadmilling
     • Model
     • In resting growth cone tubulin is dragged sporadically into filopodia
       • Happens more dramatically when in contact with an attractive cue
   • Lamella and filopodia
     • Lamella
       • Actin bundles crosslinked into a net
     • Filopodia
       • Actin bundles polarised - form larger bundles
     • Both highly motile
   • Can also be repelled
     • Semaphorins
       • Family of inhibitory molecules
       • Can be
         • membrane bound
           • E.g. retinal axons
         • Secreted
           • E.g. sema3a
           • Can cause growth cones to turn
     • Discovered when mixed cultured neurons were found to fasiculate with their own kind only
     • Watched growth cones in real time
       • Repulsed by each others axons
       • Contact led to growth cone collapse
         • Destabilises F-actin

3. Permissive substrates

   • Permissive factors
     • Also called contact attractants
   • Can define substrate paths in embryo
     • Laminin
       • Growth promoting ECM protein
         • Localised in the optic nerve
       • Does not dictate direction of axon growth
         • Just that axons can grow there
         • Blockade of laminin receptors slows growth but does not change direction
         • Gradients of laminin in vitro do not direct growth
           • In fact only permissive within specific concentration range
       • permissive but not instructive

4. Non-permissive substrates

   • Can channel axon growth
     • Mice lacking sema3a
   • Ephrins
     • Detected by eph receptors
     • Cause repulsion between cells
     • Helps compartmentalise into discrete domains
       • E.g. rhombomeres
     • Also used to keep axons out of specific areas
       • In a similar way to semaphorins
   • Also called contact repellants
     • NB. does not imply lack of adhesion

5. Chemoattractants

6. Chemorepellants

Imágenes y archivos del mapa