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The Journal of Neuroscience, May 31, 2006, 26(22):6082-6088; doi:10.1523/JNEUROSCI.4556-05.2006

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Brief Communications
Repulsive Guidance Molecule Plays Multiple Roles in Neuronal Differentiation and Axon Guidance

Eiji Matsunaga,^1,3 Harukazu Nakamura,² and Alain Chédotal¹

¹Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7102, Equipe Développement Neuronal, Université Pierre et Marie Curie-Paris 6, 75005 Paris, France, ²Department of Molecular Neurobiology, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai 980-8575, Japan, and ³Laboratory for Biolinguistics, Brain Science Institute, RIKEN, Hirosawa, Wako, 351-0918, Japan

Correspondence should be addressed to Dr. Alain Chédotal, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7102, Université Pierre et Marie Curie-Paris 6, Batiment B, case 12, 9 Quai Saint-Bernard, 75005 Paris, France. Email: chedotal{at}infobiogen.fr

Repulsive guidance molecule (RGM) is a membrane-bound protein originally isolated as a guidance molecule for retinal axons. Three RGM isoforms (RGMa–RGMc) exist in vertebrates. We showed previously that RGMa is a cell-survival factor in the neuroepithelium of chick embryos that suppresses the proapoptotic activity of its receptor neogenin. In the present study, we performed gain- and loss-of-function analysis of RGMa in chick embryos to further investigate RGMa function. We found that RGMa overexpression promotes neuronal differentiation, whereas RGMa small interference RNA represses it. Similar experiments conducted at later developmental stages using retroviral vectors reveal that perturbation of RGMa expression disturbs the retinotectal projection. Our work provides the first evidence for a role for RGMs in axon guidance in vivo. In addition, these results suggest that RGMa exerts multiple functions during neural development.

Key words: axon guidance; retinotectal; brain development; mapping; neuronal apoptosis; RNA interference

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Received Oct. 25, 2005; revised April 28, 2006; accepted April 30, 2006.

Correspondence should be addressed to Dr. Alain Chédotal, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7102, Université Pierre et Marie Curie-Paris 6, Batiment B, case 12, 9 Quai Saint-Bernard, 75005 Paris, France. Email: chedotal{at}infobiogen.fr

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