At the neuromuscular junction, the transmission of signal from the nerve to the muscle which causes muscle contraction is mediated by the release of acetylcholine from the nerve terminal and the sensing of this molecule by the receptors in the muscle. To gain insight into the formation of the neuro-muscular junction, this study will use physiological and structural techniques to observe the development of the acetylcholine receptors in the muscle cell and the development of the acetylcholine release mechanism in the nerve terminal in tissue culture and the interaction between the nerve and the muscle during innervation. We are particularly interested in the information that the nerve cell conveys to the muscle in effecting the accumulation of acetylcholine receptors in the postjunctional membrane and the mechanism that the muscle cell uses in generating such a receptor accumulation. On the presynaptic side, we are interested in the differentiation of the nerve terminal induced by its target and the mechanism of the formation of presynaptic vesicle clusters. Besides conventional nerve-muscle cocultures, we will also study the formation of the acetylcholine receptor clusters and synaptic vesicle clusters induced by basic polypeptide-coated latex beads. Previous studies from this laboratory have shown that these compounds can induce a local pre- and postsynaptic-type differentiation. These studies are aimed at providing a fundamental understanding of the development of the muscle during innervation. This knowledge is essential for the elucidation of the cause of many neuromuscular disorders.