pha-2 encodes the C. elegans ortholog of the homeodomain protein HEX and is required for the formation of the pharyngeal isthmus.
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 primordium 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.
Lundberg Laboratory, Chalmers University, Göteborg S-405 30, Sweden.
Catarina
C
Mörck
Manish
M
Rauthan
Fredrik
F
Wågberg
Marc
M
Pilon
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D007438:Introns; D008969:Molecular Sequence Data; D009154:Mutation; D010609:Pharyngeal Muscles / Q000196:embryology / Q000473:pathology; D010614:Pharynx / Q000196:embryology* / Q000473:pathology; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
C109217:CEH-22 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins; C491440:Pha-2 protein, C elegans; C113277:Pha-4 protein, C elegans; D015534:Trans-Activators; D014157:Transcription Factors