Agnieszka Trzebiatowska1, Krzysztof Drabikowski2, Ruth Chiquet-Ehrismann1. TEN-1 is a member of a novel family of transmembrane proteins named teneurins that have been characterized in Drosophila, zebrafish, chicken, mouse and man. Teneurins were shown to be mainly expressed in the developing and adult nervous system and to play a role in morphogenesis, cell migration and at sites of pattern formation. C. elegans TEN-1 was proposed to act as a receptor that signals directly to the nucleus. Its intracellular domain is cleaved and translocates to the nucleus where it may influence gene expression. Little is known, however, about the cleavage mechanism and possible target genes. C. elegans has a single teneurin orthologue, which is under control of alternative promoters. The upstream promoter is active in the somatic gonad, some muscle cells, the gut and in a number of neurons. The expression from the downstream promoter is mainly detected in the nervous system. TEN-1 is a type II transmembrane protein consisting of a short intracellular domain followed by a transmembrane domain and a long highly conserved extracellular part containing eight EGF-like repeats, a cysteine rich region and YD repeats.. In order to determine the function of TEN-1 in C.elegans, we investigated two loss-of-function mutants:
ten-1(
ok641) and
ten-1(
tm651). The former carries an in frame deletion of four EGF-like repeats and a part of the cysteine rich region; the latter has a deletion that removes the transmembrane domain and introduces a frameshift mutation resulting in the loss of the entire protein except for the first 194 aminoacids. In both mutants transcripts for the predicted truncated proteins could be detected on the level comparable to the wild type form. Both
ten-1 mutants show a pleiotropic phenotype, similar to the phenotype observed after reduction of
ten-1 expression by RNAi. Mutant worms are sterile due to various defects in the somatic gonad and ectopic germline formation in the proximity of the vulva. Time course analysis of germline development showed that these abnormalities may result from an early defect in the somatic gonad formation. We were able to partially rescue the phenotype of
ten-1(
ok641) mutant worms by injecting the cosmid F36A3 carrying the entire genomic region of the
ten-1 gene. Since such an extrachromosomal array is likely to be silenced in the germline, gonadal defects appear to be the result of impaired signaling in the somatic gonad.