Pharyngeal muscle development in the nematode Caenorhabditis elegans appears to share similarities with cardiac muscle development in other species. We have previously described CEH-22, an NK-2 class homeodomain transcription factor similar to Drosophila tinman and vertebrate Nkx2-5, which is expressed exclusively in the pharyngeal muscles. In vitro, CEH-22 binds the enhancer from
myo-2, a pharyngeal muscle-specific myosin heavy chain gene. In this paper, we examine the role CEH-22 plays in pharyngeal muscle development and gene activation by (a) ectopically expressing
ceh-22 in transgenic C. elegans and (b) examining the phenotype of a
ceh-22 loss-of-function mutant. These experiments indicate that CEH-22 is an activator of
myo-2 expression and that it is required for normal pharyngeal muscle development. However,
ceh-22 is necessary for neither formation of the pharyngeal muscles, nor for
myo-2 expression. Our data suggest parallel and potentially compensating pathways contribute to pharyngeal muscle differentiation. We also examine the relationship between
ceh-22 and the pharyngeal organ-specific differentiation gene
pha-1. Mutations in
ceh-22 and
pha-1 have strongly synergistic effects on pharyngeal muscle gene expression; in addition, a
pha-1 mutation enhances the lethal phenotype caused by a mutation in
ceh-22. Wild-type
pha-1 is not required for the onset of
ceh-22 expression but it appears necessary for maintained expression of
ceh-22.