Carl F. Lagenaur - US grants

We have discovered that a purified cell adhesion molecule, the 8D9-antigen can serve as a potent substrate for neurite growth in vitro. The 8D9-antigen is similar or identical to NILE, L1 and Ng- CAM. Using a novel in vitro assay it is now possible to further characterize the biochemical properties of the 8D9-antigen as well as begin a rational search for the 8D9-receptor. It has been demonstrated that this class of cell adhesion molecule is present during development of the nervous system but disappears in many parts of the mature nervous system. It is also known that it reappears in the regenerating peripheral nervous system. This suggests that the 8D9-antigen may serve a permissive, if not essential, role in regeneration of axon pathways. Therefore, we propose to investigate the use of this molecule as a substrate for promoting regeneration in the peripheral and central nervous systems.

The long term goal of this project is to elucidate how the activation of cAMP-dependent protein kinase following peptide hormone binding brings about a response in the cell. Specifically, the role of cAMP-dependent protein kinase in steroidogenesis and cell proliferation in Y-1, an adrenal tumor cell line, and bovine adrenal cortical cells will be studied. In this study, a specific and direct cytochemical, fluorescent, light microscopic probe and an immunogold electron microscopic procedure for localizing the subcellular sites of free catalytic and regulatory subunits will be correlated to biochemical assays of steroid secretion and cell proliferation. The results of this research will contribute to basic knowledge of the physiological role of cAMP-dependent protein kinase in triggering steroid hormone production and cell proliferation by adrenal cortical cells.

DESCRIPTION (Investigator's Abstract): The applicants plan to study conditions in the developing rodent brain necessary for supporting optic axon outgrowth and for establishing appropriate terminal connections between molecules known to support axonal outgrowth and the extension of retinal ganglion cell axons. In addition, the applicants will examine the conditions that produce optimal outgrowth and formation of connections by retinae transplanted to ectopic sites in neonatal and fetal rodent brains. One series of studies will focus on the outgrowth process itself and the substrates that support it while the other will examine what factors influence the ability of optic axons originating from transplants to innervate visual centers, to compete with other optic inputs for target space and to form topographic maps within visual centers. Such information will provide insight into how the circuitry for optimal visual function is established. It will also define the conditions necessary for creating surrogate pathways to replace damaged primary optic connections.