title: Genetic interaction between Caenorhabditis elegans teneurin ten-1 and prolyl 4-hydroxylase phy-1 and their function in collagen IV-mediated basement membrane integrity during late elongation of the embryo.
abstract: Teneurins are a family of phylogenetically conserved proteins implicated in pattern formation and morphogenesis. The sole orthologue in Caenorhabditis elegans, ten-1, is important for hypodermal cell migration, neuronal migration, path finding and fasciculation, gonad development, and basement membrane integrity of some tissues. However, the mechanisms of TEN-1 action remain to be elucidated. Using a genome-wide RNA interference approach, we identified phy-1 as a novel interaction partner of ten-1. phy-1 codes for the catalytic domain of collagen prolyl 4-hydroxylase. Loss of phy-1 significantly enhanced the embryonic lethality of ten-1 null mutants. Double-mutant embryos arrested during late elongation with epidermal defects, disruption of basement membranes, and detachment of body wall muscles. We found that deletion of phy-1 caused aggregation of collagen IV in body wall muscles in elongated embryos and triggered the loss of tissue integrity in ten-1 mutants. In addition, phy-1 and ten-1 each genetically interact with genes encoding collagen IV. These findings support a functional mechanism in which loss of ten-1, together with a reduction of assembled and secreted basement membrane collagen IV protein, leads to detachment of the epidermis from muscle cells during late elongation of the embryo when mechanical stress is generated by muscle contractions.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, and the University of Basel, Faculty of Science, Basel, Switzerland.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Topf
authors.forename: Ruth
authors.initials: R
authors.lastname: Chiquet-Ehrismann
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000002:abnormalities / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism*; D004817:Epidermis / Q000002:abnormalities / Q000378:metabolism; D004843:Epistasis, Genetic; D055785:Gene Knockdown Techniques; D005804:Genes, Lethal; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009132:Muscles / Q000002:abnormalities / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
chemical_list: D029742:Caenorhabditis elegans Proteins; D024141:Collagen Type IV; D008565:Membrane Proteins; C503009:Ten-1 protein, C elegans; D011393:Procollagen-Proline Dioxygenase