EphA/ephrin-A interactions during optic nerve regeneration: restoration of topography and regulation of ephrin-A2 expression

Mol Cell Neurosci. 2004 Jan;25(1):56-68. doi: 10.1016/j.mcn.2003.09.010.


During visual system development, interactions between Eph tyrosine kinase receptors and their ligands, the ephrins, guide retinal ganglion cell (RGC) axons to their topographic targets in the optic tectum. Here we show that Eph/ephrin interactions are also involved in restoring topography during RGC axon regeneration in goldfish. Following optic nerve crush, EphA/ephrin-A interactions were blocked by intracranial injections of recombinant Eph receptor (EphA3-AP) or phospho-inositol phospholipase-C. Topographic errors with multiple inputs to some tectal loci were detected electrophysiologically and increased projections to caudal tectum demonstrated by RT-97 immunohistochemistry. In EphA3-AP-injected fish, ephrin-A2-expressing cells in the retino-recipient tectal layers were reduced in number compared to controls and their distribution was no longer graded. The findings, supported by in vitro studies, implicate EphA/ephrin-A interactions in restoring precise topography and in regulating ephrin-A2 expression during regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / physiology
  • Cell Communication / physiology
  • Cues
  • Ephrin-A2 / genetics
  • Ephrin-A2 / metabolism*
  • Gene Expression Regulation, Developmental
  • Goldfish / physiology*
  • Growth Cones / metabolism
  • Growth Cones / ultrastructure
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology*
  • Optic Nerve / cytology
  • Optic Nerve / drug effects
  • Optic Nerve / physiology*
  • Optic Nerve Injuries / metabolism*
  • Receptor, EphA3 / genetics
  • Receptor, EphA3 / metabolism
  • Receptors, Eph Family / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Superior Colliculi / cytology
  • Superior Colliculi / growth & development
  • Superior Colliculi / metabolism
  • Type C Phospholipases / pharmacology


  • Ephrin-A2
  • Recombinant Fusion Proteins
  • Receptor, EphA3
  • Receptors, Eph Family
  • Type C Phospholipases