THE NETRINS DEFINE A FAMILY OF AXON OUTGROWTH-PROMOTING PROTEINS HOMOLOGOUS TO C-ELEGANS UNC-6

In vertebrates, commissural axons pioneer a circumferential pathway to the floor plate at the ventral midline of the embryonic spinal cord. Floor plate cells secrete a diffusible factor that promotes the outgro wth of commissural axons in vitro. We have purified from embryonic chi ck brain two proteins, netrin-1 and netrin-2, that each possess commis sural axon outgrowth-promoting activity, and we have also identified a distinct activity, that potentiates their effects. Cloning of cDNAs e ncoding the two netrins shows that they are homologous to UNC-6, a lam inin-related protein required for the circumferential migration of cel ls and axons in C. elegans. This homology suggests that growth cones i n the vertebrate spinal cord and the nematode are responsive to simila r molecular cues.