Tuesday, January 28, 2014

Axon Guidance part 2

1Growth cone cues¶

1.1Extracellular Matrix Molecules: Lamina¶

• major compoment of basal laminae
• promote axon outgrwoth
• binds to integrin on nerve cells .
• integrins bind to cytoskeletal components like actinin and talin
• guide axons to the optic nerve head (exit the retina)

1.2Adhesion molecules: CAM¶

• CAM promotes neurite growth.
• two types :
  • calcium-dependent cell adhesion molecules
  • members of immunoglobulin superfamily

1.3Ephrin¶

• temperal RGC axons project to rostral tectum
• nasal RGC project to caudal tectum

• signaling of Ephrin

  • forward: downstream of Ephs (receptors of ephrin)
  • reverse: downstream of ephrinA and B

• ephrins A :

  • high in posterior, low in anterior tectum
  • anterior-posterior tectum mapping
  • GPI-anchored, so reverse signaling possibly through recruitment of receptors

• ephrin B :

  • high in dorsal/medial and low in ventral/lateral tectum
  • transmembrane protein: reverse signaling via signaling proteins recruited to intracelluar domain

• axon guidance

  • ephrin A is repellant
    • those in nasal retina express low ephA and target toward posterior tectum
  • ephrin B is attractant
    • neurons in dorsal retina express low ephB and targets toward ventral tectum

1.4semaphorins¶

• causes growth cone to collapse
• sema5A: expressed along developing optic nerve and repels TGC axons
• prevents TGC from wandering outside of optic nerve

1.5Slits¶

• expressed at the optic chiasm
• mutation of Slit1 or slit2 leads to axonal pathfinding defects
  • ectopic chiasm, wandering axons

2Commissural Axon guidance¶

• commissural neurons project ventrally toward the floor plate, cross and turn longitudinally

2.1Netrin¶

• binds to proteoglycans, allowing cells to create gradiance
• exerts trophic effect on the axons and guide it to cross the floor plate
• aka unc-6 in worms
• unc-5 receptor: promote growth away from the midline by binding with DCC during netrin signaling
• unc-40: DCC in mammals, promote growth toward midline

3Intracellular signaling¶

• siganling through rho : growth cone collapse , repulsion
  • semaphorin, ephrin A
• signaling through rac or cdc42: promote growth cones, attraction
  • netrin, slit