Domain-specific olivocerebellar projection regulated by the EphA-ephrin-A interaction

Kazuhiko Nishida, John G. Flanagan, Masaru Nakamoto

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Neural maps in the vertebrate central nervous system often show discontinuously segregated, domain-to-domain patterns. However, the molecular mechanism that establishes such maps is not well understood. Here we show that in the chicken olivocerebellar system, EphA receptors and ephrin-As are expressed with distinct levels and combinations in mapping domains. When ephrin-A2 is retrovirally overexpressed in the cerebellum, the olivocerebellar map is disrupted, excluding axons with high receptor activity from ectopic expression domains. Conversely, overexpression of a truncated EphA3 receptor in the cerebellum reduces endogenous ligand activity to undetectable levels and causes aberrant mapping, with high receptor axons invading high ligand domains. In vitro, ephrin-A2 inhibits outgrowth of inferior olive axons in a region-specific manner. These results suggest that Eph receptors and ephrins constitute domain-specific positional information, and the spatially accurate receptor-ligand interaction is essential to guide inferior olive axons to their correct target domains.

Original languageEnglish
Pages (from-to)5647-5658
Number of pages12
JournalDevelopment
Volume129
Issue number24
DOIs
Publication statusPublished - 15 Dec 2002

Keywords

  • Eph receptors
  • ephrins
  • olivocerebellar projection
  • CNS
  • developing chick cerebellum
  • retinal axon guidance
  • ganglion-cell axons
  • tyrosine kinase
  • visual-system
  • lateral position
  • purkinje-cells
  • ROBO receptors
  • in-vitro
  • expression

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