Boc is a receptor for sonic hedgehog in the guidance of commissural axons.
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.
Okada
Ami
A
Department of Biological Sciences, Stanford University, Stanford, California 94305, USA. amio@stanford.edu
Charron
Frédéric
F
Morin
Steves
S
Shin
David S
DS
Wong
Karen
K
Fabre
Pierre J
PJ
Tessier-Lavigne
Marc
M
McConnell
Susan K
SK
D000818:Animals; D001369:Axons / Q000502:physiology*; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D053823:Hedgehog Proteins / Q000378:metabolism*; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism
C510745:Boc protein, mouse; C510744:Cdon protein, mouse; D015815:Cell Adhesion Molecules; D053823:Hedgehog Proteins; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface