Members of the spalt (sal) gene family encode zinc-finger proteins that are putative tumor suppressors and regulate anteroposterior (AP) patterning, cellular identity, and, possibly, cell cycle progression. The mechanism through which sal genes carry out these functions is unclear. The Caenorhabditis elegans sal gene
sem-4 controls the fate of several different cell types, including neurons, muscle and hypodermis. Mutation of
sem-4 transforms particular tail neurons into touch-neuron-like cells. In wild-type C. elegans, six touch receptor neurons mediate the response of the worm to gentle touch. All six touch neurons normally express the LIM homeobox gene
mec-3. A subset, the two PLM cells, also express the Hox gene
egl-5, an Abdominal-B homolog, which we find is required for correct
mec-3 expression in these cells. The abnormal touch-neuron-like-cells in
sem-4 animals express
mec-3; we show that a subset also express
egl-5. We report: (1) that ectopic expression of
sem-4 in normal touch cells represses
mec-3 expression and reduces touch cell function; (2) that
egl-5 expression is required for both the fate of normal PLM touch neurons in wild-type animals and the fate of a subset of abnormal touch neurons in
sem-4 animals, and (3) that SEM-4 specifically binds a shared motif in the
mec-3 and
egl-5 promoters that mediates repression of these genes in cells in the tail. We conclude that
sem-4 represses
egl-5 and
mec-3 through direct interaction with regulatory sequences in the promoters of these genes, that
sem-4 indirectly modulates
mec-3 expression through its repression of
egl-5 and that this negative regulation is required for proper determination of neuronal fates. We suggest that the mechanism and targets of regulation by
sem-4 are conserved throughout the sal gene family: other sal genes might regulate patterning and cellular identity through direct repression of Hox selector genes and