Establishment of the uniquely specific cell-cell interactions required in nervous systems almost certainly requires the participation of unique cell surface components. The ability of neuronal cells to distinguish themselves from others, migrate to specific sites, and elaborate specialized functional connections is likely to be related to the synthesis and expression of complex arrays of cell membrane-associated macromolecules. While cell surface constituents must play important roles in establishing cellular identity and in regulating specific cell-cell interactions, relatively little is known concerning the biochemical nature of such molecules or their mechanism of action. During recent studies of the binding of fluorescein-conjugated lectins to developing mouse retina, it was observed that peanut lectin (PNA) binds specifically to cone photoreceptors cells. The binding is most intense in the cone outer segment region and in discrete, possible synaptic, regions of the inner and outer plexiform layers of the retina. These results indicate the existence of significant cellular and regional hetero-geneity in the distribution of glycoconjugate molecules within the retina, and suggest the possibility that PNA-binding glycoproteins might be employed as specific molecular markers for cone photoreceptors and their synapses. The proposed studies will examine a possible role for PNA-binding molecules in establishing the biochemical basis of neuronal specificity in the retina. The molecules responsible for the cone-specific binding of PNA in the retina will be characterized biochemically and purified by lectin affinity chromatography. Specific polyclonal and monoclonal antibodies directed against specific PNA-binding glycoproteins will be developed and used to monitor the expression of specific molecular species during cellular differentiation and synaptogenesis in the retina. Ultrastructural studies will identify the cellular and subcellular correlates of PNA binding. The results of these studies should provide new data of significance in our understanding of the molecular and genetic basis of neural cell development of function.