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Teneurins in development and disease

Kenzelmann Broz, Daniela. Teneurins in development and disease. 2008, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_8563

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Abstract

The teneurins are a novel type II transmembrane protein family
originally discovered in Drosophila and highly conserved between invertebrates
and vertebrates. Studies in invertebrates suggest important functions for the
teneurins in many processes during development. However, still very little is
known about the biological function and mechanism of action of the vertebrate
teneurin family, which consists of four paralogs called teneurin-1 to -4.
In the first part of my thesis, I analyzed the expression pattern and
signaling mechanism of teneurin-1 during chick development. Teneurin-1 was
prominently expressed in specific regions of the brain, and often complementary
to teneurin-2. The presence of teneurin-1 and -2 in interconnected regions of
the brain implies a role for teneurins in the establishment of appropriate
neuronal connectivity. Using a novel antibody recognizing the teneurin-1
intracellular domain (ICD), N-terminal processing products were detected and
nuclear staining was observed in specific neurons and tissues. This provides
evidence for our working hypothesis, according to which teneurins can be
processed by a mechanism called regulated intramembrane proteolysis,
resulting in the release and nuclear translocation of the ICD. Similar results
were obtained for teneurin-4 during chick development.
In the second part of my thesis, I investigated the implication of
teneurins in two human diseases.
X-linked mental retardation: Teneurin-1 was analyzed as an X-linked
mental retardation (XLMR) candidate gene in 23 XLMR patients. No mutation
that is likely to cause the disease was found the coding region or splice sites of
the teneurin-1 gene in these patients.
Brain tumors: Teneurin-4 was found to be upregulated in a microarray
analysis of human brain tumors including astrocytomas, oligodendrogliomas and
glioblastomas (GBMs). The overexpression of teneurin-4 was confirmed on
protein level in brain tumor lysates. Immunohistochemistry (IHC) revealed
strong staining around tumors cells in some brain tumors whereas in others
teneurin-4 restricted to blood vessels.
Advisors:Chiquet-Ehrismann, Ruth
Committee Members:Rüegg, Markus A. and Hynes, Nancy
Faculties and Departments:09 Associated Institutions > Friedrich Miescher Institut FMI
UniBasel Contributors:Kenzelmann Broz, Daniela and Rüegg, Markus A.
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:8563
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:120
Language:English
Identification Number:
Last Modified:22 Apr 2018 04:30
Deposited On:08 Apr 2009 18:32

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