NEUROLIN, THE GOLDFISH HOMOLOG OF DM-GRASP, IS INVOLVED IN RETINAL AXON PATHFINDING TO THE OPTIC DISK

Young axons of new retinal ganglion cells (RGCs) in the continuously g rowing goldfish retina fasciculate with one another and their immediat e forerunners on their path toward the optic disk and along the optic nerve. They express the immunoglobulin superfamily cell adhesion molec ules (CAMs) neurolin (DM-GRASP) and the L1-like E587 antigen. Repeated injections of Fab fragments from polyclonal antisera against neurolin (neurolin Fabs) into the eye of 3.4-cm-long and rapidly growing goldf ish caused highly aberrant pathways of young RGC axon subfascicles in the dorsal retina. Many axons grew in circles and failed to reach the optic disk. In contrast, E587 Fabs, used in parallel experiments, disr upted the fascicles but did not interfere with the disk-directed growt h. Neurolin Fabs also disturbed axonal fasciculation in vivo as well a s in vitro but less severely than E587 Fabs. Coinjections of both Fabs increased defasciculation of the dorsal axons in both aberrant and di sk-directed routes. They also disrupted the order of young RGC axons i n the optic nerve more severely than E587 Fabs alone. This demonstrate s that the development of tight and orderly fascicles in the dorsal re tina and in the optic nerve requires both E587 antigen and neurolin. M ore importantly, our results suggest an involvement of neurolin in RGC axonal guidance from the retinal periphery to the optic disk. Because disrupted fascicles and errant axon routes were found only in the dor sal retinal half, a cooperation with so-called positional markers may be conceived.