The
pha-2 mutant was isolated in 1993 by Leon Avery in a screen for worms with visible defects in pharyngeal feeding behavior. In
pha-2 mutant worms, the pharyngeal isthmus is abnormally thick and short and, in contrast to wild-type worms, harbors several cell nuclei. We show here that
pha-2 encodes a homeodomain protein and is homologous to the vertebrate homeobox gene, Hex (also known as Prh). Consistent with a function in pharyngeal development, the
pha-2 gene is expressed in the pharyngeal primordiurn of Caenorhabditis elegans embryos, particularly in
pm5 cells that form the bulk of the isthmus. We show that in the
pha-2 mutant there is a failure of the
pm5 cells to elongate anteriorly while keeping their nuclei within the nascent posterior bulb to form the isthmus during the 3-fold embryonic stage. We also present evidence that
pha-2 regulates itself positively in
pm5 cells, that it is a downstream target of the forkhead gene
pha-4, and that it may also act in the isthmus as an inhibitor of the
ceh-22 gene, an Nkx2.5 homolog. Finally, we have begun characterizing the regulation of the
pha-2 gene and find that intronic sequences are essential for the complete
pha-2 expression profile. The present report is the first to examine the expression and function of an invertebrate Hex homolog, that is, the C. elegans
pha-2 gene.