Netrin-1 is required for the normal development of spinal cord oligodendrocytes

Successful CNS myelination is dependent on the correct localization of oligodendrocytes and their interactions with adjacent axons. In the spinal cord, oligodendrocyte precursors originate at the ventral midline and subsequently migrate to the white matter where they mature. In vitro studies suggest this dispersal is mediated by the guidance molecule netrin-1. Here, we show that in the spinal cord of netrin- 1 mutant mice, oligodendrocyte precursors failed to disperse from the ventral midline as a consequence of a lack of polarization and directional migration. The lack of netrin- 1 also resulted in an overall reduction of oligodendrocyte lineage cells that was independent of the failure of initial dispersal. Oligodendrocyte precursors injected into presumptive white matter underwent extensive radial migration and expansion in wild-type but not netrin-1 mutant hosts. These data indicate that netrin- 1 is crucial for both the initial dispersal of spinal cord oligodendrocyte precursors and their subsequent development in the presumptive white matter.