THE CAENORHABDITIS-ELEGANS NK-2 HOMEOBOX GENE CEH-22 ACTIVATES PHARYNGEAL MUSCLE GENE-EXPRESSION IN COMBINATION WITH PHA-1 AND IS REQUIRED FOR NORMAL PHARYNGEAL DEVELOPMENT

Pharyngeal muscle development in the nematode Caenorhabditis elegans a ppears to share similarities with cardiac muscle development in other species, We have previously described CEH-22, an NK-2 class homeodomai n transcription factor similar to Drosophila tinman and vertebrate Nkx 2-5, which is expressed exclusively in the pharyngeal muscles, In vitr o, 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 pla ys in pharyngeal muscle development and gene activation by (a) ectopic ally expressing ceh-22 in transgenic C. elegans and (b) examining the phenotype of a ceh-22 loss-of-function mutant, These experiments indic ate that CEH-22 is an activator of myo-2 expression and that it is req uired for normal pharyngeal muscle development, However, ceh-22 is nec essary for neither formation of the pharyngeal muscles, nor for myo-2 expression, Our data suggest parallel and potentially compensating pat hways contribute to pharyngeal muscle differentiation. We also examine the relationship between ceh-22 and the pharyngeal organ-specific dif ferentiation gene pha-1. Mutations in ceh-22 and pha-1 have strongly s ynergistic 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 expre ssion but it appears necessary for maintained expression of ceh-22.