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.