Kinase independent function of EphB receptors in retinal axon pathfinding to the optic disc from dorsal but not ventral retina

Eric Birgbauer, Chad A. Cowan, David W. Sretavan, Mark Henkemeyer

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

Optic nerve formation requires precise retinal ganglion cell (RGC) axon pathfinding within the retina to the optic disc, the molecular basis of which is not well understood. At CNS targets, interactions between Eph receptor tyrosine kinases on RGC axons and ephrin ligands on target cells have been implicated in formation of topographic maps. However, studies in chick and mouse have shown that both Eph receptors and ephrins are also expressed within the retina itself, raising the possibility that this receptor-ligand family mediates aspects of retinal development. Here, we more fully document the presence of specific EphB receptors and B-ephrins in embryonic mouse retina and provide evidence that EphB receptors are involved in RGC axon pathfinding to the optic disc. We find that as RGC axons begin this pathfinding process, EphB receptors are uniformly expressed along the dorsal-ventral retinal axis. This is in contrast to the previously reported high ventral-low dorsal gradient of EphB receptors later in development when RGC axons map to CNS targets. We show that mice lacking both EphB2 and EphB3 receptor tyrosine kinases, but not each alone, exhibit increased frequency of RGC axon guidance errors to the optic disc. In these animals, major aspects of retinal development and cellular organization appear normal, as do the expression of other RGC guidance cues netrin, DCC, and L1. Unexpectedly, errors occur in dorsal but not ventral retina despite early uniform or later high ventral expression of EphB2 and EphB3. Furthermore, embryos lacking EphB3 and the kinase domain of EphB2 do not show increased errors, consistent with a guidance role for the EphB2 extracellular domain. Thus, while Eph kinase function is involved in RGC axon mapping in the brain, RGC axon pathfinding within the retina is partially mediated by EphB receptors acting in a kinase-independent manner.

Original languageEnglish (US)
Pages (from-to)1231-1241
Number of pages11
JournalDevelopment
Volume127
Issue number6
StatePublished - Mar 2000

Fingerprint

Eph Family Receptors
Retinal Ganglion Cells
Optic Disk
Retina
Phosphotransferases
Ephrins
Axons
EphB3 Receptor
EphB2 Receptors
Brain Mapping
Ligands
Axon Guidance
Optic Nerve
Protein-Tyrosine Kinases
Cues
Embryonic Structures

Keywords

  • Axon guidance
  • Eph receptors
  • Ephrins
  • Growth cones
  • Retinal ganglion cells
  • Tyrosine kinase
  • Visual system

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Kinase independent function of EphB receptors in retinal axon pathfinding to the optic disc from dorsal but not ventral retina. / Birgbauer, Eric; Cowan, Chad A.; Sretavan, David W.; Henkemeyer, Mark.

In: Development, Vol. 127, No. 6, 03.2000, p. 1231-1241.

Research output: Contribution to journalArticle

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