title: 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.
abstract: 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.
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, 60607, USA. okkema@uic.edu
authors.forename: P G
authors.initials: PG
authors.lastname: Okkema
authors.forename: E
authors.initials: E
authors.lastname: Ha
authors.forename: C
authors.initials: C
authors.lastname: Haun
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Fire
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D010609:Pharyngeal Muscles / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: C109217:CEH-22 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C094797:vnd protein, Drosophila