1. Department of Biological Sciences, Stanford University, Stanford, California 94305, USA
2. Institut de recherches cliniques de Montréal (IRCM), 110 avenue des Pins Ouest, Montreal, Quebec H2W 1R7, Canada
3. Department of Medicine, University of Montreal, Montreal, Quebec, Canada
4. Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA
5. These authors contributed equally to this work.
6. Present address: Department of Neurology, Stanford University School of Medicine, Stanford, California 94305, USA.

Correspondence to: Ami Okada^1,5,6 Correspondence and requests for materials should be addressed to A.O. (Email: amio@stanford.edu).

Abstract

In the spinal cord, sonic hedgehog (Shh) is secreted by the floor plate to control the generation of distinct classes of ventral neurons along the dorsoventral axis¹. Genetic and in vitro studies have shown that Shh also later acts as a midline-derived chemoattractant for commissural axons². However, the receptor(s) responsible for Shh attraction remain unknown. Here we show that two Robo-related proteins, Boc and Cdon, bind specifically to Shh and are therefore candidate receptors for the action of Shh as an axon guidance ligand. Boc is expressed by commissural neurons, and targeted disruption of Boc in mouse results in the misguidance of commissural axons towards the floor plate. RNA-interference-mediated knockdown of Boc impairs the ability of rat commissural axons to turn towards an ectopic source of Shh in vitro. Taken together, these data suggest that Boc is essential as a receptor for Shh in commissural axon guidance.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.