Neurons and their targets must exchange morphogenetically important information as synapses are formed, maintained and modified. Our goals are to identify some of the factors in skeletal muscle that influence the behavior of motor axons, and to learn how they regulate and are regulated by synaptic interactions. Recent experiments have shown that some of these factors are associated with basal lamina (BL) that ensheaths each muscle fiber and runs between nerve and muscle at the neuromuscular junction; synaptic portions of the BL can organize the differentiation of regenerating axons into nerve terminals and may guide selective reinnervation of original synaptic sites following nerve damage. We have obtained antibodies to muscle fiber BL that reveal differences between its synaptic and extrasynaptic portions. In addition, we have used immunochemical methods to study the expression of several previously identified adhesive macromolecules in muscle, and suggested that muscles may use a medley of these molecules to influence regenerating axons. These antibodies will be used as histochemical stains and as high- affinity ligands to study the composition, function and development of the muscle fiber surface (membrane, BL, and matrix). Specifically, we propose to; (1) Isolate and characterize components of synaptic BL that we have defined with monoclonal antibodies and lectins. (2) Use cell surface components and antibodies to them in blocking experiments, to elucidate roles of individual adhesive molecules. (3) Study the regulation of these cell surface molecules during formation of neuromuscular junctions in rat embryos. (4) Initiate a search for molecules that muscles may use to bias synapse formation with positionally matched motor axons. Through this work, we hope to gain some insight into how muscles use cell surface molecules to determine patterns of innervation.
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