The broad objectives of our project are to identify and investigate the molecules that mediate the formation and differentiation of synapses. We have focused on the basal lamina, an extracellular structure that can direct pre- and postsynaptic differentiation at the neuromuscular junction. We have previously made genetic variants of muscle cells that produce a defective form of proteoglycans, a component of the basal lamina, and have shown that one of these variants is deficient in aspects of both pre- and postsynaptic differentiation. We propose to develop immunological, biochemical and molecular tools to isolate and characterize the molecules involved. We will also use hybrid myotubes and nerve-muscle co-cultures to investigate the mechanisms by which these molecules exert their effects on acetylcholine receptor clustering and on the growth and differentiation of presynaptic neurites.
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