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doi: 10.1242/10.1242/dev.00162

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Development 129, 5647-5658 (2002)
Copyright © 2002 The Company of Biologists Limited

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

Kazuhiko Nishida1, John G. Flanagan2 and Masaru Nakamoto1,*

1 Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
2 Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA

* Author for correspondence (e-mail: nakamom{at}ccf.org)

Accepted 11 September 2002

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.

Key words: Eph receptors, Ephrins, Olivocerebellar projection, CNS






© The Company of Biologists Ltd 2002