The control of muscle contraction and human movement relies on the establishment of precise connections between motor neurons in the brain and spinal cord and the skeletal muscles. During embryonic development, motor nerves make contact with muscle cells and induce the muscle membrane to form a specialized domain called the neuromuscular junction. At the neuromuscular junction, many protein molecules including the nicotinic acetylcholine receptor, rapsyn, utrophin, and dystroglycans, are highly concentrated. These molecules are assembled into a large complex, termed the postsynaptic apparatus. The postsynaptic apparatus is critically important for the transmission of brain signals from motor nerves to muscles, and for the maintenance of normal muscle structure and function. Disruption of the protein complex is known to cause many neuromuscular diseases including myasthenia gravis, muscular dystrophy, and etc. The principal investigator of this research project will investigate the molecular mechanism that governs the development of postsynaptic apparatus at the neuromuscular junction. He will test the hypothesis that both the formation and maintenance of the postsynaptic protein machinery are critically dependent upon a recently identified molecule, called Adenomatous Polyposis Coli (APC). APC acts as a scaffold to organize and stabilize the membrane protein complex by tethering it to the cytoskeleton at neuromuscular junction. Two sets of experiments have been proposed. First, a genetic approach to determine whether deletion of the APC gene is detrimental to the structure and function of neuromuscular synapse in mouse embryos will be performed. Second, the question whether the APC protein has a physiological role in the development and maintenance of nerve-muscle connections in postnatal and adult life will be examined.
The research will create unique opportunities for postdoctoral fellows, graduate and undergraduate students to learn and study the process of how neurons in the brain make precise connections with their target tissues during development. The novel concepts, approaches, and techniques of the projects will be taught in various summer programs to train high school and minority students for advanced biological research.
