The eucaryotic cell surface has been implicated in the control of cell adhesion, growth, motility, and morphology. Presumably, this is accomplished via specific cell surface receptors which "sense" the cell's environment and allow the cell to respond accordingly. These control mechanisms are central in the process of morphogenesis, and in neoplastic transformation and metastasis. The most highly regulated example of cell surface interactions may be the vertebrate nervous system, where neurons may be coded to make specific connections with appropriate target cells. The elucidation of the molecular basis of cell surface interactions remains a major challenge. This proposal investigates the role of a prominent class of cell surface molecules --complex carbohydrates (particularly glycosphingolipids (GSL)) -- in controlling cell surface interactions in neuronal cells. Cloned neuronal tissue culture cells and cells dissociated from embryonic neural tissue will be employed. Two major approaches will be used: 1. Interactions of intact neurons with GSL and synthetic carbohydrates immobilized on matrixes. Exposure of intact cells to synthetic carbohydrates immobilized on inert plastic surfaces has been used to elicit carbohydrate-specific cellular responses. This novel technique will be used to directly test the ability of particular complex carbohydrates to direct adhesion, growth, motility, and morphology of primary and clonal neuronal cells in tissue culture. Techniques will be developed to identify specfic GSL and carbohydrate receptors on neuronal cell surfaces. 2. Metabolism of glycosphingolipids in neuronal cells. A hybrid neuroblastoma x glioma cell line which displays, in vitro, many developmental and regulatory characteristics of nerve cells in vivo will be used to study the content and metabolism of GSL in response to controlled differentiation and specific cell-cell interactions. Correlations between cell surface carbohydrate structures and cell differentiation will be investigated.