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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1726-1733. Prepublished online as a Blood First Edition Paper on May 12, 2005; DOI 10.1182/blood-2005-01-0337. This Article Full Text (PDF) All Versions of this Article: 2005-01-0337v1 106/5/1726    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Goux, D. Articles by Held, W. Search for Related Content PubMed PubMed Citation Articles by Goux, D. Articles by Held, W. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 31, 2005 Accepted May 2, 2005 Cooperating pre-T cell receptor and TCF-1-dependent signals ensure thymocyte survival Delphine Goux, Jerome D Coudert, Diane Maurice, Leonardo Scarpellino, Gregoire Jeannet, Stefano Piccolo, Kathleen Weston, Joerg Huelsken, and Werner Held* Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland Cancer Research UK Centre for Cell & Molecular Biology, Institute of Cancer Research, London, United Kingdom Department of Histology, Microbiology and Medical Biotechnology, University of Padua, Padua, Italy Institut Suisse de Recherche Experimentale sur le Cancer (ISREC), Epalinges, Switzerland * Corresponding author; email: wheld{at}isrec.unil.ch. Intrathymic T cell maturation critically depends on the selective expansion of thymocytes expressing a functionally rearranged T cell receptor (TCR) chain. In addition, TCR-independent signals also contribute to normal T cell development. It is unclear whether and how signals from the two types of pathways are integrated. Here, we show that T cell factor-1 (TCF-1), a nuclear effector of the canonical wnt/catenin signaling pathway, ensures the survival of proliferating, pre-TCR+ thymocytes. The survival of pre-TCR+ thymocytes requires the presence of the N-terminal catenin-binding domain in TCF-1. This domain can bind the transcriptional co-activator -catenin and may also bind -catenin (plakoglobin). However, in the absence of -catenin, T cell development is normal, supporting a role for -catenin. Signaling competent -catenin is present prior to and thus arises independently from pre-TCR signaling and does not substantially increase upon preTCR signaling. In contrast, pre-TCR signaling significantly induces TCF-1 expression. This coincides with the activation of a wnt/catenin/TCF reporter transgene in vivo. Collectively, these data suggest that efficient TCF-dependent transcription requires that preTCR signaling increases TCF-1 expression whereas wnt signals may provide the co-activator such as -catenin. The two pathways thus have to cooperate to ensure thymocyte survival at the pre-TCR stage. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Kovalovsky, Y. Yu, M. Dose, A. Emmanouilidou, T. Konstantinou, K. Germar, K. Aghajani, Z. Guo, M. Mandal, and F. Gounari {beta}-Catenin/Tcf Determines the Outcome of Thymic Selection in Response to {alpha}{beta}TCR Signaling J. Immunol., September 15, 2009; 183(6): 3873 - 3884. [Abstract] [Full Text] [PDF] N. J. Rowbotham, A. L. Hager-Theodorides, A. L. Furmanski, S. E. Ross, S. V. Outram, J. T. Dessens, and T. Crompton Sonic hedgehog negatively regulates pre-TCR-induced differentiation by a Gli2-dependent mechanism Blood, May 21, 2009; 113(21): 5144 - 5156. 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