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

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.

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Figure 1: Boc is expressed by young commissural neurons undergoing axon guidance decisions in the spinal cord.
Figure 2: Aberrant axon targeting in Boc -/- but not Cdon -/- spinal cord.
Figure 3: Boc and Cdon bind directly to Shh.
Figure 4: Boc is required for commissural axons to respond to the chemoattractive effect of Shh.

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Acknowledgements

We thank L. Luo, A. O’Reilly, M. Scott and K. Shen for critically reading the manuscript; C. Jolicoeur and H. Rayburn for the generation of chimaeric mice; C. Kaznowski for technical assistance; R. Krauss, J. Zhang, M. Scott, H. Tian and F. de Sauvage for discussions during early stages of the project; and T. Rando for supporting A.O. during the writing of the manuscript. This work was supported by grants from the National Institute of Mental Health and American Cancer Institute to A.O., the National Eye Institute to S.K.M., the National Institute of Mental Health to M.T.L. and S.K.M., and the Arnold and Mabel Beckman Foundation, the Fonds de Recherche en Santé du Québec (FRSQ), the Canadian Institutes of Health Research (CIHR) and the Peter Lougheed Medical Research Foundation to F.C.

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Correspondence to Ami Okada.

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Okada, A., Charron, F., Morin, S. et al. Boc is a receptor for sonic hedgehog in the guidance of commissural axons. Nature 444, 369–373 (2006). https://doi.org/10.1038/nature05246

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