The
mec-3 gene encodes a transcription factor involved in development of the touch neurons of C. elegans.
mec-3 is necessary for the specification and maintenance of the six touch receptor neurons and two other pairs of neurons, the PVD and FLP cells. The fact that
mec-3 is required for the differentiation of three different classes of cells indicates that the gene is subject to combinatorial control. Several different genes (
unc-86,
mec-17,
sem-4, and
mec-3 itself) have been implicated in control of
mec-3 function and expression. The MEC-3 protein is composed of two LIM domains, a homeodomain, and an acidic region. Each of these regions likely mediates different protein-protein interactions that modulate MEC-3 function. The UNC-86 protein has been shown to bind to a region of MEC-3 just C-terminal of the homeodomain (1) . I am interested in answering three questions about MEC-3 function and regulation. First, what additional genes are involved in combinatorial control of
mec-3 ? Second, how, specifically, do known
mec-3 regulators carry out their functions? Third, what are the functions of the different regions of MEC-3? I will try two different approaches to answer these questions: ectopic expression of a putative repressor of
mec-3 and the yeast two hybrid screen.
sem-4 is a zinc finger transcription factor required for the development of several different types of neurons, including the PHC cells (2, 3) .
sem-4 mutant animals produce two additional cells in the tail that exhibit touch-cell characteristics; these cells may arise from lineages that would normally generate PHC neurons (2) . Because the development of these extra neurons is
mec-3 dependent, and because PHC neurons do not normally express
mec-3, it is possible that SEM-4 negatively regulates MEC-3 in these cells. I am in the process of expressing SEM-4 ectopically in the touch cells to see if this expression can render animals touch insensitive perhaps by interfering with development of the touch cells. I plan to screen a yeast two hybrid library to identify molecules that interact with MEC-3, in particular, with the LIM domains. In the meantime, I am attempting to characterize some putative MEC-3 interacting proteins pulled out of a prior two hybrid screen using the MEC-3 LIM domains as bait. One of these molecules has since been cloned and identified as UNC-97, a molecule composed almost entirely of five LIM domains (4) . I am using genetic crosses to establish whether the MEC-3/UNC-97 interaction is functionally significant. 1. Xue, D., Tu, Y., and Chalfie, M. (1993). Cooperative interactions between the Caenorhabditis elegans homeoproteins UNC-86 and MEC-3. Science, 261, 1324-1328. 2. Basson, M. and Horvitz, H.R. (1996). The Caenorhabditis elegans gene
sem-4 controls neuronal and mesodermal cell development and encodes a zinc finger protein. Genes & Dev., 10, 1953-1965. 3. Mitani, S., Du, H., Hall, D.H., Driscoll, M., and Chalfie, M. (1993). Combinatorial control of touch receptor neuron expression in Caenorhabditis elegans. Development, 119, 773-783. 4. Hobert, O., Moerman, D., Liu, X., and Ruvkun, G. (1998). A PINCH of LIM domains in UNC-97 et al. The Worm Breeder's Gazette, 15, 40-41.