The molecular basis of retinotectal topography

Over 50 years have passed since Roger Sperry formulated a simple model of how visual space, as seen by the retina, can be projected onto the brain in a two-dimensional, topographic map during development. Sperry posited a set of two orthogonal gradients in the retina that gives each cell a positional identity. He further suggested that these molecules could be used to match up with complementary gradients in the target field of the retinal projection, the tectum. While some investigators hold that the existence of such molecules may not be necessary to establish retinotectal maps, recent work has identified several cell surface proteins whose distributions are of the type predicted by Sperry. An unexpected twist comes from culture assays demonstrating that inhibitory activities on tectal membranes can guide the growth of processes from retinal neurons. Moreover, the expression patterns of several enzymes and three transcription factors suggest that these proteins are candidates for regulatory agents in the determination of cell position in the retina. In addition, results from perturbation experiments support the candidacy of two of the enzymes, and a new mutant screen has uncovered several as yet unidentified genes that are required for establishment of the proper retinotectal map. A number of these results were presented at a recent meeting on neurospecificity held in Cargese, Corsica and sponsored by NATO and NSF.