Agnieszka Trzebiatowska

Friedrich Miescher Institute for Biomedical Research, Bâle, Basel-City, Switzerland

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Publications (3)12.06 Total impact

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    ABSTRACT: The Caenorhabditis elegans teneurin ortholog, ten-1, plays an important role in gonad and pharynx development. We found that lack of TEN-1 does not affect germline proliferation but leads to local basement membrane deficiency and early gonad disruption. Teneurin is expressed in the somatic precursor cells of the gonad that appear to be crucial for gonad epithelialization and basement membrane integrity. Ten-1 null mutants also arrest as L1 larvae with malformed pharynges and disorganized pharyngeal basement membranes. The pleiotropic phenotype of ten-1 mutant worms is similar to defects found in basement membrane receptor mutants ina-1 and dgn-1 as well as in the mutants of the extracellular matrix component laminin, epi-1. We show that the ten-1 mutation is synthetic lethal with mutations of genes encoding basement membrane components and receptors due to pharyngeal or hypodermal defects. This indicates that TEN-1 could act redundantly with integrin INA-1, dystroglycan DGN-1, and laminin EPI-1 in C. elegans development. Moreover, ten-1 deletion sensitizes worms to loss of nidogen nid-1 causing a pharynx unattached phenotype in ten-1;nid-1 double mutants. We conclude that TEN-1 is important for basement membrane maintenance and/or adhesion in particular organs and affects the function of somatic gonad precursor cells.
    Preview · Article · Sep 2008 · Molecular biology of the cell
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    ABSTRACT: Teneurins are a novel family of transmembrane proteins expressed during pattern formation and morphogenesis. Originally discovered as ten-m and ten-a in Drosophila, four vertebrate teneurins as well as a Caenorhabditis elegans homologue were identified. The conserved domain architecture of teneurins includes an intracellular domain containing polyproline motifs. The long extracellular domain consists of eight EGF-like repeats, a region of conserved cysteines and unique YD-repeats. Vertebrate teneurins are most prominently expressed in the developing central nervous system, but are also expressed in developing limbs. In C. elegans, RNAi experiments and studies of mutants reveal that teneurins are required during fundamental developmental processes like cell migration and axon pathfinding. Cell culture experiments suggest that the intracellular domain of teneurins translocates to the nucleus following release from the membrane by proteolytic processing. Interestingly, the human teneurin-1 gene is located on the X-chromosome in a region where several families with X-linked mental retardation are mapped.
    No preview · Article · Feb 2007 · The International Journal of Biochemistry & Cell Biology
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    Krzysztof Drabikowski · Agnieszka Trzebiatowska · Ruth Chiquet-Ehrismann
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    ABSTRACT: ten-m (odz) is the only pair-rule gene discovered in Drosophila that encodes a transmembrane protein and not a transcription factor. The vertebrate Ten-m orthologues have been implicated in pattern formation and neuronal development. To investigate the role of this protein in development, we characterize here the structure and function of the Caenorhabditis elegans orthologue ten-1. We found that two promoters control the expression of two different ten-1 transcripts. This results in the expression of type II transmembrane protein variants differing in their intracellular domains. Both ten-1 transcripts show complex, but distinct, expression patterns during development and in the adult. Interference with Ten-1 expression by RNAi experiments leads to multiple phenotypes resulting in defects in hypodermal cell migration, neuronal migration, pathfinding and fasciculation, distal tip cell migration, the establishment of the somatic gonad, and gametogenesis. The RNAi phenotypes were confirmed by the analysis of a deletion mutant which revealed that Ten-1 is essential for somatic gonad formation. The intracellular domain of the long form was detected at the cell membrane and in the nucleus. We propose that Ten-1 acts as a receptor for morphogenetic cue(s) and directly signals to the nucleus by translocation of its intracellular domain to the nucleus following its proteolytic release from the cell membrane.
    Preview · Article · Jul 2005 · Developmental Biology