Loss-of-Function Analysis of EphA Receptors in Retinotectal Mapping

David A. Feldheim, Masaru Nakamoto, Miriam Osterfield, Nicholas W. Gale, Thomas M. DeChiara, Rajat Rohatgi, George D. Yancopoulos, John G. Flanagan

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

EphA tyrosine kinases are thought to act as topographically specific receptors in the well-characterized projection map from the retina to the tectum. Here, we describe a loss-of-function analysis of EphA receptors in retinotectal mapping. Expressing patches of a cytoplasmically truncated EphA3 receptor in chick retina caused temporal axons to have reduced responsiveness to posterior tectal repellent activity in vitro and to shift more posteriorly within the map in vivo. A gene disruption of mouse EphA5, replacing the intracellular domain with β-galactosidase, reduced in vitro responsiveness of temporal axons to posterior target membranes. It also caused map abnormalities in vivo, with temporal axons shifted posteriorly and nasal axons anteriorly, but with the entire target still filled by retinal axons. The anterior shift of nasal axons was not accompanied by increased responsiveness to tectal repellent activity, in contrast to the comparable anterior shift in ephrin-A knock-outs, helping to resolve a previous ambiguity in interpreting the ephrin gene knock-outs. The results show the functional requirement for endogenous EphA receptors in retinotectal mapping, show that the receptor intracellular domain is required for a forward signaling response to topographic cues, and provide new evidence for a role of axon competition in topographic mapping.

Original languageEnglish (US)
Pages (from-to)2542-2550
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number10
DOIs
StatePublished - Mar 10 2004

    Fingerprint

Keywords

  • Axon
  • Eph
  • Ephrin
  • Receptor
  • Retina
  • Topographic

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Feldheim, D. A., Nakamoto, M., Osterfield, M., Gale, N. W., DeChiara, T. M., Rohatgi, R., Yancopoulos, G. D., & Flanagan, J. G. (2004). Loss-of-Function Analysis of EphA Receptors in Retinotectal Mapping. Journal of Neuroscience, 24(10), 2542-2550. https://doi.org/10.1523/JNEUROSCI.0239-03.2004