The overall objective of this project is to obtain a more detailed description of the role of cell-cell interactions in the development of the eye. The major focus of this work is the neural cell adhesion molecule (NCAM), which is a broadly distributed cell surface protein whose binding properties and unusual polysialic acid (PSA) moiety influence a wide variety of cell interactions. The strategy has two phases: make observations of relevant fundamental mechanisms in model systems, and then apply this knowledge to the study of the eye. The fundamental topics addressed in this proposal are the migration and positioning of cells, the formation of specialized intercellular junctions, and promotion of target-dependent changes in neuronal biochemistry. The systems in which these events are to be studied are the retina, lens, and ciliary ganglion, each comprising one of the specific aims. The proposed experiments involve a multidisciplinary approach, including antibody-mediated perturbation of NCAM function, enzymatic knockout of PSA using a specific endoneuraminidase (endo N), and analysis of the NCAM-mutant mice generated in the applicant's laboratory. Because the normal function of the eye requires such precision in its tissue architecture and physiology, its systems are particularly sensitive to malformation and damage. The studies in this project are relevant to a fundamental understanding of the formation of the retina, establishment of ciliary ganglion input to the muscles of the iris, and to development of the lens.
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