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

Catarina Mörck,Marc Pilon,Gholamali Jafari,Vivekanand Vivekanand

doi:10.1186/1471-213x-10-55

Catarina Mörck, Marc Pilon + Show 2 more

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https://doi.org/10.1186/1471-213x-10-55

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Abstract

BackgroundTeneurins are transmembrane proteins that assist morphogenetic processes in many organisms. ten-1 is the C. elegans teneurin homolog with two transcripts, ten-1a and ten-1b, that respectively encode a long (TEN-1L) and short (TEN-1S) form of the protein. We previously isolated a C. elegans mutant where one pharyngeal neuron was frequently misplaced, and now show that it corresponds to a novel allele of ten-1.ResultsThe 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.ConclusionsOur 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.

Highlights

Teneurins are transmembrane proteins that assist morphogenetic processes in many organisms. ten-1 is the C. elegans teneurin homolog with two transcripts, ten-1a and ten-1b, that respectively encode a long (TEN-1L) and short (TEN-1S) form of the protein
We found that the novel ten-1(et5) allele exhibits the same rate of embryonic lethality as the null alleles (~6%), but reduced incidence of post-embryonic phenotypes, such that over 70% of homozygous et5 progeny grow into fertile adults (Table 1). ten-1(et5) is not a null allele, which suggests an important function for the four EGF repeats present in the ten-1(et5) allele but absent from the tm651 and ok641 alleles
To determine if other pharyngeal neurons depend on functional ten-1 for their development, we examined the trajectories of the pharyngeal neurons for which we could obtain specific GFP reporters in both the ten-1(et5) and the more severe ten-1(ok641) mutants

Summary

Introduction

Teneurins are transmembrane proteins that assist morphogenetic processes in many organisms. ten-1 is the C. elegans teneurin homolog with two transcripts, ten-1a and ten-1b, that respectively encode a long (TEN-1L) and short (TEN-1S) form of the protein. Teneurins are transmembrane proteins that assist morphogenetic processes in many organisms. The Drosophila homologs, Ten-m and Ten-a, are the only pair-rule genes that do not encode traditional transcription factors [3,4,5]. 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. The distinct expression profiles of various teneurins or teneurin isoforms in vertebrates, together with the neuronal defects observed in mutants, strongly suggest that teneurins act during cell communication to influence neurite outgrowth and guide axons [1,8,9]. Biochemical studies on the four mouse teneurins (Ten-m1 to Ten-m4) have shown that the EGF domains are important for teneurin homo- or heterodimerization via covalent disulfide links between the second and fifth EGF repeats [10,11], while the NHL and YD repeats form large glycosylated globular domains that may mediate homotypic or heterotypic interactions between cells that express the same or different forms of teneurin, as well as interactions with the extracellular matrix [1,2]

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