Beckmann, Jan. Teneurin evolution and brain-specific functions. 2012, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10027
In the first part of the thesis, I am presenting a study of the possible evolutionary origins of teneurins, identifying a teneurin-like gene in the choanoflagellate Monosiga brevicollis. Furthermore, alternative splicing of the intracellular domain and conservation of nuclear localization sequences and protease cleavage sites were analyzed.
In the second part of the thesis, I analyzed the transcriptional regulation of human teneurin�1, contributing to its patterned expression in the brain. I found a novel conserved alternate promoter, upstream of the annotated transcription start. The transcription factor Emx2 directly binds to a single conserved homeobox binding site in this novel promoter, in vitro and in vivo and Emx2 is able to activate teneurin-1 expression in reporter assays, as well as on the endogenous level.
In the third part of the thesis, I investigated the homophilic interactions of teneurins, using an atomic force microscope (AFM) as a single cell force spectroscope (SCFS). This showed that the intracellular domain is essential for mediating adhesion forces, established by homophilic interactions by the extracellular domains. The NHL repeats of teneurins located in the large extracellular part between the EGF-like repeats and the YD-repeats are essential in discriminating homophilic versus heterophilic interactions. Finally, I could show that the homophilic interactions mediated by the NHL domains provide a signal for slowing down neurite outgrowth of Nb2a cells.
|Committee Members:||Tucker, Richard P. and Pielage, Jan|
|Faculties and Departments:||09 Associated Institutions > Friedrich Miescher Institut FMI|
|Bibsysno:||Link to catalogue|
|Number of Pages:||84 Bl.|
|Last Modified:||30 Jun 2016 10:49|
|Deposited On:||23 Aug 2012 09:50|
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