Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system.
During nervous system development, spinal commissural axons project toward floor plate cells and trochlear motor axons extend away from these cells. Netrin-1, a diffusible protein made by floor plate cells, can attract spinal commissural axons and repel trochlear axons in vitro, but its role in vivo is unknown. Netrin-1 deficient mice exhibit defects in spinal commissural axon projections that are consistent with netrin-1 guiding these axons. Defects in several forebrain commissures are also observed, suggesting additional guidance roles for netrin-1. Trochlear axon projections are largely normal, predicting the existence of additional cues for these axons, and evidence is provided for a distinct trochlear axon chemorepellent produced by floor plate cells. These results establish netrin-1 as a guidance cue that likely collaborates with other diffusible cues to guide axons in vivo.