A large collection of clonal nerve, glial, and muscle cell lines will be used in conjunction with primary cultures to examine problems related to the development of the nervus system. The roles of extracellular macromolecules in cellular adhesion, matrix assembly, and the differentiation of several cell types will be defined. Emphasis will be placed upon the neural retina. The role of cell-cell and cell-matrix interactions in the cellular differentiation and tissue cytoarchitecture of the neural retina will be examined in both chick and rodents by the use of immunological and molecular biological techniques. The participation of newly identified extracellular glycoprotein complexes, termed adherons, in the above processes will be studied. One 20,000 MW protein found only in the adherons of embryonic chick neural retina is responsible for the adheron-cell adhesion and the survival of cultured neural retina cells. These effects occur by virtue of its specific interaction with a heparan sulfate proteoglycan cell surface receptor. The heparan sulfate binding protein will be sequenced by molecular cloning techniques and its structure and function determined. In addition to the neural retina, extracellular molecules will be studied in cultured nerve, muscle, and glia. The stimulatory role of adherons from smooth muscle in the adhesion of sympathetic nerve cells will be examined, and the molecules responsible for these interactions identified. The extracellular molecules released by regenerating sciatic nerve in vivo will be studied with respect to their effects on Schwann cell migraton, adhesion, and differentiation.
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