FORMATION AND ELIMINATION OF NERVE-MUSCLE SYNAPSES

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The formation of patterned connections between motor neurons and muscles during development in the vertebrates requires specific cell-cell recognition as well as an editing mechanism of synaptic elimination. The complex anatomy of even this relatively simple system is such that an understanding of these phenomena at the cellular and molecular levels is difficult. The leg neuromuscular system of the cockroach is even simpler with muscles innervated by one or a small number of motor neurons. When the axons of these motor neurons are cut, they regenerate and eventually reform synapses with just the original target muscles. However, at early stages of regeneration inappropriate synapses form. The apparent specificity arises from the selective elimination of these mistakes. The cockroach serves as a model system in which to examine common developmental processes at the cellular and molecular levels. The ability to distinguish among target muscles indicates that there are molecular differences between individual motor neurons and between individual muscles. Monoclonal antibodies are available that bind to the surfaces of axon terminals of identified motor neurons. These will be used to purify the antigens and to demonstrate a function for them during regeneration. Tissue culture and immunohistochemical techniques will be used to test the hypothesis that the specificity of the interaction between motor neurons and muscles arises from a selective enhancement of growth and sprouting of axons only in their appropriate target muscles. Recombinant DNA techniques will be used to characterize the candidate recognition macromolecules. The information acquired on the mechanism of the successful regeneration of cockroach motor neurons will also be applicable to attempts to increase the probability of obtaining such regeneration in humans. Such knowledge would be helpful for the treatment of paraplegia, neuromuscular disorders, multiple sclerosis and other neurological disorders involving injury such as strokes and head injury.