Žalac, Tatjana. The role of the transcription factor Sox9 for thymic epithelial cell differentation and function. 2011, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_9587
In the present study, we demonstrate that Sox9, which is differentially expressed in the thymus by non-hematopoietic stromal cells, negatively regulates TEC proliferation and inversely correlates with the expression of the transcription factor Foxn1. The TEC-targeted loss of Sox9 disturbs thymus genesis and results in a hypoplastic thymus with a phenotypically altered epithelial compartment. Mice with a TEC-targeted Sox9 deficiency display subset-specific changes in TEC composition and proliferation, a phenotype which correlates with an upregulation of Foxn1 expression. Despite these alterations, thymopoiesis remains unaffected indicating that Sox9 expression is not required for the TEC`s capacity to support T cell development. In vitro studies revealed that Sox9 regulates Foxn1 transcription indirectly by binding and regulating the amount of intracellular β-catenin protein. This correlation suggests a crosstalk between Sox9 and the canonical Wnt pathway to occur in thymic epithelia.
To our best of knowledge, this study provides the first functional evidence that Sox9 controls TEC proliferation and differentiation in a dose-sensitive and subset-specific manner and negatively regulates Foxn1 expression in TEC. Although, the loss of Sox9 expression in TEC is not sufficient to jeopardize T cell development, differential Sox9 expression is critical for the establishment and maintenance of a regular thymic microenvironment.
|Advisors:||Holländer, Georg A.|
|Committee Members:||Rolink, Antonius G.|
|Faculties and Departments:||03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Pädiatrische Immunologie (Holländer)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||140 S.|
|Last Modified:||30 Jun 2016 10:42|
|Deposited On:||02 Sep 2011 10:01|
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