The primary goal of this proposal is to identify factors that guide retinal ganglion cell axons out of the eye and along their stereotyped routes to the brain during development and regeneration. The focus of this research is the neural cell adhesion molecule (NCAM) which appears to be directly involved in the attraction and guidance of pioneering optic axons within specialized regions of their non-neuronal environment. In our initial studies on chick embryos we have found a preformed array of NCAM on neuroepithelial cell endfeet that temporally and spatially foreshadows the route of optic axons (Silver and Rutishauser in press, and appendix 1). Following on these observations, the specific aims of this proposal are designed to further explore (1) the developmental events that lead to the formation and maintenance of the NCAM pathway as well as boundary regions that lack NCAM; (2) how abnormalities of endfeet or NCAM expression can lead to congenital axonal malformations in the retina and optic nerve of ocular retardation and albino mutants, (3) how the modulation of NCAM on endfeet could influence the success or failure of retinal ganglion cell axon regeneration and (4) why intraocular injection of anti-NCAM Fab in the living embryo causes dramatic retinal and optic nerve malfunctions in addition to altering axon pathways. It is hoped that these studies will lead to a better understanding of the role of adhesion mediated cell-cell interactions in normal and abnormal development as well as in regeneration of the vertebrate optic system.
