"Caenorhabditis elegans" TEN-1 is essential for basement membrane function.
PhD Thesis, University of Basel,
Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_8238
Teneurins are large transmembrane proteins playing fundamental roles in development. They are highly expressed in the developing and adult nervous system in distinct layers, often in interconnected regions of the brain, where they were proposed to have an important function during target recognition and synapse formation. Beside the nervous system, teneurins are found at places of cell migration, at morphogentically active zones in developing limbs or at muscle attachment sites. The extracellular domains of teneurins interact in a homophilic manner and this interaction may trigger release of the intracellular domain from the membrane. The soluble intracellular domain can translocate to the nucleus and influence gene expression. To elucidate teneurin function, we studied the role of the single teneurin orthologue ten-1 in C. elegans development. We characterized mutants in the ten-1 gene and found that TEN-1 is important for gonad development, vulva formation, distal tip cell migration and axonal guidance. Despite of such pleiotropic phenotypes, we initially concentrated on the gonadal defects. We found that ten-1 does not control germline proliferation but is essential for the maintenance of the gonadal basement membrane. The basement membrane defect in the ten-1 mutant was very local and most of the basement membranes showed generally wild-type ultrastructure as analyzed by electron microscopy. Similar disorganization of early gonads has been reported for integrin ina-1, dystroglycan dgn-1 and laminin epi-1 mutant worms. Therefore, we took a candidate gene approach and tested the genetic interactions between ten-1 and genes encoding various basement membrane proteins and receptors. This analysis revealed that teneurin acts redundantly with integrin and dystroglycan. Moreover, mutation in ten-1 sensitized the worms to loss of nidogen and led to defects in pharyngeal morphogenesis. Genetic studies also indicated that laminin could be a ligand for TEN-1 but initial data from vertebrate in vitro studies have not confirmed this hypothesis. Reporter constructs showed TEN-1 localization in the cytoplasm and membrane of certain head neurons, pharynx and several gonadal cells but no signs of nuclear translocation of the teneurin intracellular domain could be detected. Our data provide the first evidence for a novel role of teneurin in basement membrane biology and its redundant function with integrin and dystroglycan receptors.
|Committee Members:||Affolter, Markus|
|Faculties and Departments:||09 Associated Institutions > Friedrich Miescher Institut FMI|
|Bibsysno:||Link to catalogue|
|Number of Pages:||118|
|Last Modified:||30 Jun 2016 10:41|
|Deposited On:||13 Feb 2009 16:41|
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