The purpose of this study is to use immunological techniques to identify and characterize molecules which either promote axon elongation during the development of the central nervous system (CNS) or inhibit elongation in the adult CNS. Using methods to manipulate the immune response, we have generated 40 monoclonal antibodies to embryonic CNS-specific antigens and 31 to antigens that appear late in the developing CNS. The antibodies that bind to embryonic CNS tissues will be used in vitro assays to determine if their respective antigens might function in axon elongation during the development of the CNS and whether these antigens are reexpressed following injury to the CNS. Antibodies that bind to adult CNS, but not to embryonic CNS tissues, will be tested for their ability to enhance neurite growth in culture. Two different bioassays will be used to identify antigens which influence neurite growth. First, dissociated neurons will be plated onto cryostat sections of hippocampus and cerebellum and second, transformed glial cell lines will be produced and co-cultured with primary neurons. Antibodies which either inhibit or promote neurite growth in these bioassays will be used to characterize the corresponding antigens. Antibodies which do not directly block neurite growth, but which recognize antigens whose spatial and temporal expression is coordinated with axon growth in vivo, may prove valuable for analyzing the cell biology of axon growth.
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