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The Journal of Neuroscience, July 15, 2002, 22(14):5992-6004
Directional Guidance of Oligodendroglial Migration by Class 3 Semaphorins and Netrin-1
Nathalie Spassky1, *, Fernando de Castro1, 3, *, Barbara Le Bras1, *, Katharina Heydon1, Françoise Quéraud-LeSaux1, Evelyne Bloch-Gallego2, Alain Chédotal2, Bernard Zalc1, and Jean-Léon Thomas1 1 Biologie des Interactions Neurones, Glie Institut National de la Santé et de la Recherche Médicale (INSERM) U-495 and 2 INSERM U-106, Université Pierre et Marie Curie, IFR des Neurosciences, Hôpital de la Salpêtrière, 75651 Paris, France, and 3 Neurobiología, Department de Investigación, Hospital Ramón y Cajal, E-28034 Madrid, Spain
Oligodendrocytes, the myelin-forming cells of the CNS, are generated from multiple foci distributed along the developing neural tube. Little is known about the endogenous guidance cues controlling the migration of oligodendrocyte precursor cells (OPCs) from their site of emergence toward their final destination, mainly the future white matter tracts. During embryonic development, the optic nerve is populated by OPCs originating in the diencephalon that migrate from the chiasm toward the retina. Here we show that OPCs migrating into the embryonic optic nerve express the semaphorin receptors neuropilin-1 and -2, as well as deleted in colorectal cancer (DCC) and, to a lesser extend unc5H1, two of the netrin-1 receptors. Using a functional migration assay, we provide evidence that Sema 3A and netrin-1 exert opposite chemotactic effects, repulsive or attractive, respectively, on embryonic OPCs. In addition, we show that Sema 3F has a dual effect, chemoattractive and mitogenic on embryonic OPCs. The localization of cells expressing Sema 3A, Sema 3F, and netrin-1 is consistent with a role for these ligands in the migration of OPCs in the embryonic optic nerve. Altogether, our results suggest that the migration of OPCs in the embryonic optic nerve is modulated by a balance of effects mediated by members of the semaphorin and netrin families.
Key words: cell migration; class 3 semaphorins; multiple sclerosis; myelin; netrin-1; oligodendrocyte; optic nerve
* N.S., F.d., and B.L. have contributed equally to this paper.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22145992-13$05.00/0
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