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Stabilized beta-catenin in thymic epithelial cells blocks thymus development and function

Zuklys, Saulius and Gill, Jason and Keller, Marcel P. and Hauri-Hohl, Mathias and Zhanybekova, Saule and Balciunaite, Gina and Na, Kyung-Jae and Jeker, Lukas T. and Hafen, Katrin and Tsukamoto, Noriyuki and Amagai, Takashi and Taketo, Makoto M. and Krenger, Werner and Holländer, Georg A.. (2009) Stabilized beta-catenin in thymic epithelial cells blocks thymus development and function. Journal of immunology : official journal of the American Association of Immunologists, Vol. 182. pp. 2997-3007.

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Official URL: http://edoc.unibas.ch/dok/A6005632

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Abstract

Thymic T cell development is dependent on a specialized epithelial microenvironment mainly composed of cortical and medullary thymic epithelial cells (TECs). The molecular programs governing the differentiation and maintenance of TECs remain largely unknown. Wnt signaling is central to the development and maintenance of several organ systems but a specific role of this pathway for thymus organogenesis has not yet been ascertained. In this report, we demonstrate that activation of the canonical Wnt signaling pathway by a stabilizing mutation of beta-catenin targeted exclusively to TECs changes the initial commitment of endodermal epithelia to a thymic cell fate. Consequently, the formation of a correctly composed and organized thymic microenvironment is prevented, thymic immigration of hematopoietic precursors is restricted, and intrathymic T cell differentiation is arrested at a very early developmental stage causing severe immunodeficiency. These results suggest that a precise regulation of canonical Wnt signaling in thymic epithelia is essential for normal thymus development and function.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Pediatric Immunology (Holländer)
UniBasel Contributors:Krenger, Werner and Holländer, Georg
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Assoc. of Immunologists
ISSN:0022-1767
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2013 11:14
Deposited On:01 Mar 2013 11:11

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