DESCRIPTION: The principal investigator will continue studies of factors controlling neuronal differentiation in the nematode Caenorhabditis elegans. Most of the research will center, as in the past, on the analysis of neuronal differentiation of a set of six touch receptor neurons (the touch cells). Previous research under this grant has led to the identification of over 500 mutations that render the animal touch insensitive. These mutations define 17 genes needed for the generation, specification, maintenance, and function of the touch cells. The homeodomain products of two of the regulatory genes, mec-3 and unc-86, form heterodimers that are needed to promote touch cell differentiation. The combinatorial action of seven other genes, however, are needed to restrict touch cell differentiation to six cells in wild-type animals. In the upcoming grant period the investigators will study how this combinatorial control specifies touch cell fate, uncover new touch-cell- specific genes by a newly developed, differential screening method, and identify genes whose products are needed for synaptic specificity. The specific aims of the proposal are: 1) To characterize the combinatorial regulation of touch cell fate; 2) To identify and characterize new mec-3- dependent genes; 3) To investigate the maintenance of touch cell differentiation; 4) To identify and characterize genes needed for neuronal outgrowth and synapse specification.