C. elegans ten-1 is synthetic lethal with mutations in cytoskeleton regulators, and enhances many axon guidance defective mutants

The novel ten-1(et5) allele is a hypomorph since its post-embryonic phenotype is weaker than the null alleles ten-1(ok641) and ten-1(tm651). ten-1 mutants have defects in all pharyngeal neurons that we examined, and in vivo reporters show that only the long form of the ten-1 gene is expressed in the pharynx, specifically in six marginal cells and the M2 neurons. Defects in the pharyngeal M2 neurons were enhanced when the ten-1(ok641) mutation was combined with mutations in the following genes: mig-14, unc-5, unc-51, unc-52 and unc-129. None of the body neurons examined show any defects in the ten-1(ok641) mutant, but genetic interaction studies reveal that ten-1(ok641) is synthetic lethal with sax-3, unc-34 and unc-73, and examination of the hypodermal cells in embryos of the ten-1(ok641) mutant point to a role of ten-1 during hypodermal cell morphogenesis.Our results are consistent with ten-1 normally providing a function complementary to the cytoskeletal remodeling processes that occur in migrating cells or cells undergoing morphogenesis. It is possible that ten-1 influences the composition/distribution of extracellular matrix.Teneurins are transmembrane proteins that participate in morphogenetic processes in many organisms [1,2]. Teneurins have a single transmembrane domain, a very large and cleavable extracellular domain containing eight EGF repeats, four NHL domains and more than 20 YD repeats, as well as a cleavable intracellular domain (ICD) that can be translocated to the nucleus. The Drosophila homologs, Ten-m and Ten-a, are the only pair-rule genes that do not encode traditional transcription factors [3-5]. Instead, they act at the cellular blastoderm stage, and cleavage of the ICD may allow it to directly regulate the transcription of target genes in alternate parasegments. Drosophila Ten-m is also important for several other developmental processes, including retina development [6], and peripheral nervous system development in imaginal disc-derived organ