NETRIN-1 IS REQUIRED FOR COMMISSURAL AXON GUIDANCE IN THE DEVELOPING VERTEBRATE NERVOUS-SYSTEM

During nervous system development, spinal commissural axons project to ward floor plate cells and trochlear motor axons extend away from thes e 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 defec ts in spinal commissural axon projections that are consistent with net rin-1 guiding these axons. Defects in several forebrain commissures ar e also observed, suggesting additional guidance roles for netrin-1. Tr ochlear axon projections are largely normal, predicting the existence of additional cues for these axons, and evidence is provided for a dis tinct trochlear axon chemorepellent produced by floor plate cells. The se results establish netrin-1 as a guidance cue that likely collaborat es with other diffusible cues to guide axons in vivo.