Investigations on the functions ot "ten-1" during embryonic development in "Caenorhabditis" elegans

Topf, Ulrike. Investigations on the functions ot "ten-1" during embryonic development in "Caenorhabditis" elegans. 2011, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_9585

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Teneurins are a family of phylogenetically conserved proteins. Their most prominent site of expression is the nervous system. Investigations on the expression pattern in vertebrates and invertebrates also revealed the importance for teneurins at sites of morphogenesis during embryonic development. Nevertheless, the function of teneurins remains to be discovered. Teneurins are type II transmembrane proteins. The mechanism of action of teneurins involves the translocation of the intracellular domain into the nucleus. It is postulated that the release of the intracellular domain requires several proteolytic events in the extracellular part, the transmembrane domain and at the cytosolic part. The stimulus of these events is unclear, but there is evidence for homophilic interactions between the teneurins.
The advantage of C. elegans as a model organism to investigate the function and mechanism of action of teneurins is that the C. elegans genome codes only for a single ortholog of the vertebrate teneurins. Two different promoters give rise to at least two different transcript versions. The promoters show distinct patterns of activity in the mesoderm and in the ectoderm of the worm. Two independent deletion mutants are characterized as null mutations. Knock-down by RNAi and analysis of the null mutants revealed that ten-1 is essential for embryonic development but also for postembryonic events like larval development and reproduction. Interestingly, investigations on potential genetic interaction partners of ten-1 uncovered functional redundancy between ten-1 and basement membrane associated genes coding for homologs of integrin, dystroglycan, laminin, nidogen and perlecan. Co-staining of chicken teneurin and laminin in some tissues during embryonic development might point to an evolutionary conserved function of teneurins associated with the basement membrane.
In this study I used a genome wide approach to obtain a comprehensive list of potential genetic interaction partners of ten-1. I characterized the interaction with phy-1 in more detail. phy-1 is conserved among the phyla and codes for the catalytical domain of the collagen-modifying enzyme prolyl 4-hydroxylase. I found that loss of phy-1 in the ten-1 null mutant background enhances embryonic lethality significantly. Worms die during late elongation because of loss of connectivity between muscles, epidermis and the separating basement membrane. In addition, I present evidence that the function of PHY-1 modifying basement membrane collagen IV is conserved also in C. elegans.
Advisors:Chiquet-Ehrismann, Ruth
Committee Members:Affolter, Markus
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Affolter)
UniBasel Contributors:Affolter, Markus
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:9585
Thesis status:Complete
Number of Pages:128 S.
Identification Number:
Last Modified:22 Jan 2018 15:51
Deposited On:02 Sep 2011 09:48

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