DIFFERENTIAL WITHDRAWAL OF RETINAL AXONS INDUCED BY A SECRETED FACTOR

To understand the development of the topographic map in the chick reti notectal projection, we studied the long-term interactions between ret inal axons and tectal cell processes using a novel coculture system, t he ryomen chamber. Both nasal and temporal retinal axons initially gre w equally well on a substrate consisting of posterior tectal cell proc esses; however, subsequently most temporal axons withdrew from this su rface, whereas most nasal axons did not. Experiments using conditioned media indicate that posterior tectal cells induced withdrawal of the temporal axons by secreting a soluble factor. This withdrawal seems to be distinct from the immediate repulsive effect of ephrin-A2 (ELF-1) and ephrin-A5 (RAGS) seen in the stripe assay because (1) the withdraw al-inducing factor was diffusible, whereas ephrin-A2 and -A5 are membr ane-bound, and (2) the withdrawal-inducing factor appeared later in de velopment than ephrin-A2 and -A5. Furthermore, sensitivity to the with drawal-inducing factor decreased continuously from the temporal to nas al retina. These results suggest that target cell-induced axonal withd rawal may be involved during a late stage of the development of the re tinotectal map.