DETERMINANTS OF OPTIC AXON OUTGROWTH

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An antibody has been identified to a cell surface protein, designated M6, which blocks neurite outgrowth in vitro. Studies on the developing optic nerve in vivo indicate that M6 is expressed only up to a certain critical period of development. The biological function in vitro and the pattern of expression in vivo suggested that by knowing more about the behavior of the antigen and its antibody, we would gain further insight into why optic axons stop growing during development and why they generally fail to regenerate after injury. Additional results collected over the past year confirm this expectation and indicate that a substantial investigation of the antigen and its antibody centered on the primary optic pathway is justified. This proposal focuses on three areas: (1) We wish to examine the hypothesis that the antigen is involved in vivo with the processes of axonal growth and cell migration. (2) We wish to use the antibody to arrest irreversibly both cell migration and axonal outgrowth as a tool for studying various interdependencies occurring during development and after injury. (3) We wish to examine how the context in which a neuron develops may regulate the expression of the M6 antigen and as a result modify neurite outgrowth and cell migration patterns. Nine individual experiments are proposed, each of which addresses one or more of the three areas raised. Collectively, they should provide insight into the behavior in vivo of an antigen which appears to regulate neurite extension by a molecular mechanism which is under investigation in parallel studies. They will also exploit the use of the antibody both as a probe and a label for investigating plasticity and regeneration of the visual system.