Neuronal connections between visual centers are laid out as if homologous points within topographical maps are interconnected. Sperry's chemoaffinity hypothesis postulates that this address system is generated in the early embryo through a system of two graded properties in the retina, one in the antero-posterior and the other in the dorso-ventral dimension, which match up with corresponding graded properties in the optic targets. We identified a system that might be involved in the generation of the dorso-ventral axis of the map: an antigen in the dorsal part of the undifferentiated embryonic retina which very likely represents a configuration of the high-affinity laminin receptor. This receptor, which is principally studied for its role in cancer metastasis, occurs in several molecular weight forms, which we propose to investigate with a combination of immunological, biochemical, molecular and cell-biological means. We are asking whether this molecule serves other functions in addition to laminin binding, and which of its possible functions may be relevant for the dorso-ventral axis of the retina. Species who use binocular vision need in addition to the system that sets up retinal topography a system that assures the partial crossing of retinofugal projections: the exact division of the retina at a line corresponding to the midline of the visual field into crossed and uncrossed projections. This line of decussation is defective in mutants with less than normal amounts of melanin in the retinal pigment epithelium. Through anatomical tracings in the embryo we will determine when this line is formed, and with a combination of methods, including generation of antibodies and neuronal explant assays, we will search for factors that may underlie a presumed repulsive action on the uncrossed projections at the midline of the brain. As melanin pigment represents one of the largest calcium buffers, we hope to eventually test the hypothesis that the mechanism for partial decussation involves a calcium-sensitive step which is influenced by the amount of melanin in the retinal pigment epithelium.
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