NETRIN-1 AND DCC MEDIATE AXON GUIDANCE LOCALLY AT THE OPTIC DISC - LOSS OF FUNCTION LEADS TO OPTIC-NERVE HYPOPLASIA

Embryonic retinal ganglion cell (RGC) axons must extend toward and gro w through the optic disc to exit the eye into the optic nerve. in the embryonic mouse eye, we found that immunoreactivity for the axon guida nce molecule netrin-1 was specifically on neuroepithelial cells at the disk surrounding exiting RGC axons, and RGC axons express the netrin receptor, DCC (deleted in colorectal cancer). In vitro, anti-DCC antib odies reduced RGC neurite outgrowth responses to netrin-1. In netrin-1 - and DCC-deficient embryos, RGC axon pathfinding to the disc was unaf fected; however, axons failed to exit into the optic nerve, resulting in optic nerve hypoplasia. Thus, netrin-1 through DCC appears to guide RGC axons locally at the optic disc rather than at long range, appare ntly reflecting the localization of netrin-1 protein to the vicinity o f netrin-1-producing cells at the optic disc.