The long-term objective of this proposal is to understand how genes specify the structure, functioning, and development of a behavioral network. Toward this end, the anatomically simple egg-laying system of the small free-living nematode Caenorhabditis elegans will be analyzed genetically. Mutants abnormal in egg-laying will be isolated both to define the components of the egg-laying system and to define the genes that affect those components. The pleiotropies of these mutants should reveal how single cells can affect multiple behaviors and also how single genes can affect multiple cells. The functional roles of neurons implicated in egg-laying by anatomical and/or genetical studies will be tested by surgically removing those neurons using a laser microbeam. Detailed studies of mutations that affect the HSN motoneurons, which innervate the vulval musculature, should increase our understanding of how nervous system development and complexity are specified in the genome: for example, it should be possible to define a genetic pathway for the generation, differentiation and functioning of this specific neuron type as well as to determine the extent, to which single genes are specific for single neurons. Both genetic and molecular studies will reveal the times and sites of expression of particular genes necessary for HSN development and functioning and may help elucidate the molecular bases of how mutations can affect behavior. Such knowledge may prove relevant to an understanding of human genetic behavioral disorders. In addition, information gained from these studies concerning basic nematode behavior and neurobiology could help in the prevention and/or treatment of diseases caused by parasitic nematodes, which are a major source of human suffering in the world today.
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