The C. elegans Hox gene lin-39 encodes a homeodomain-containing protein similar to the Drosophila Deformed and Sex Combs Reduced proteins, lin-39 is expressed in the C. elegans mid-body region, including the vulval precursor cells, and is required for the proper fate determination of these cells. In these vulval precursor cells, the tin-39 gone is coordinately regulated by both Wnt and Ras signaling pathways. We propose that the Hox gene lin-39 in C. elegans functions as a transcriptional regulator that controls the expression of a set of downstream genes in order to control the fates of the vulval precursor cells. We propose experiments to 1) determine how the Wnt and Ras pathways regulate LIN-39 protein levels, 2) identify LIN-39 binding sites in vitro and assay their relevance in vivo, 3) determine whether phosphorylation alters the functions of LIN-39 in vitro or in vivo, and 4) identify and characterize target genes regulated by L1N-39 using a microarray -based approach. Hox proteins such as LIN-39 are known to function in the patterning of cells along the anterior-posterior axis during the development of all metazoans, and defects in Hox gone expression can lead to drastic defects in development. Although Hox proteins have been characterized in many species, only a handful of target genes have been identified for these proteins. Therefore much can be learned about the function of this important class of master developmental control genes in all organisms, including humans, by the characterization of Hox protein targets in the model system C. elegans, for which full genomic sequence is available and functional genomic approaches are available. ? ?
