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.

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Vascular endothelial growth factor C (VEGF-C) was first identified as a regulator of the vascular system, where it is required for the development of lymphatic vessels. Here we report actions of VEGF-C in the central nervous system. We detected the expression of the VEGF-C receptor VEGFR-3 in neural progenitor cells in Xenopus laevis and mouse embryos. In Xenopus tadpole VEGF-C knockdowns and in mice lacking Vegfc, the proliferation of neural progenitors expressing VEGFR-3 was severely reduced, in the absence of intracerebral blood vessel defects. In addition, Vegfc-deficient mouse embryos showed a selective loss of oligodendrocyte precursor cells (OPCs) in the embryonic optic nerve. In vitro, VEGF-C stimulated the proliferation of OPCs expressing VEGFR-3 and nestin-positive ventricular neural cells. VEGF-C thus has a new, evolutionary conserved function as a growth factor selectively required by neural progenitor cells expressing its receptor VEGFR-3.