Boc is a receptor for sonic hedgehog in the guidance of commissural axons

• Published in: Nature (London) Vol. 444; no. 7117; pp. 369 - 373
• Main Authors: Charron, Frédéric, Shin, David S, Fabre, Pierre J, McConnell, Susan K, Morin, Steves, Wong, Karen, Okada, Ami, Tessier-Lavigne, Marc
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 16.11.2006; Nature Publishing Group
• Subjects: Animals; Axons - physiology; Biological and medical sciences; Cell Adhesion Molecules - deficiency; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cercopithecus aethiops; COS Cells; Fundamental and applied biological sciences. Psychology; Gene expression; General aspects. Models. Methods; Genetics; Hedgehog Proteins - metabolism; Immunoglobulin G - genetics; Immunoglobulin G - metabolism; Mice; Neurosciences; Protein Binding; Proteins; Receptors, Cell Surface - deficiency; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; RNA Interference; Rodents; Spinal cord; Spinal Cord - cytology; Spinal Cord - metabolism; Vertebrates: nervous system and sense organs; Spinal cord; Rat; Rodentia; Central nervous system; Interference; Axon; In vitro; Protein; Guidance; Vertebrata; Mammalia; Neuron; Mouse; Animal; Biological receptor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature05246

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 axis. Genetic and in vitro studies have shown that Shh also later acts as a midline-derived chemoattractant for commissural axons. 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.