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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 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 Citation Map 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. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Cooperating pre–T-cell receptor and TCF-1–dependent signals ensure thymocyte survival Delphine Goux, Jérôme D. Coudert, Diane Maurice, Leonardo Scarpellino, Grégoire Jeannet, Stefano Piccolo, Kathleen Weston, Joerg Huelsken, and Werner Held From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland; the Cancer Research UK Centre for Cell & Molecular Biology, Institute of Cancer Research, London, United Kingdom; the Department of Histology, Microbiology and Medical Biotechnology, University of Padua, Padua, Italy; and the Institut Suisse de Recherche Expérimentale sur le Cancer (ISREC), Epalinges, Switzerland. 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 2 types of pathways are integrated. Here, we show that T-cell factor-1 (TCF-1), a nuclear effector of the canonical wingless/int (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 coactivator -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 on pre-TCR 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 pre-TCR signaling induces TCF-1 expression, whereas wnt signals may provide the coactivator such as -catenin. The 2 pathways thus have to cooperate to ensure thymocyte survival at the pre-TCR stage. (Blood. 2005;106:1726-1733) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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. [Abstract] [Full Text] [PDF] M. Xu, A. Sharma, D. L. Wiest, and J. M. 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Birnbaum, J. C. Rathmell, and G. A. Koretzky Akt1 and Akt2 are required for {alpha}beta thymocyte survival and differentiation PNAS, July 17, 2007; 104(29): 12105 - 12110. [Abstract] [Full Text] [PDF] Q. Yu, M. Xu, and J. M. Sen beta-Catenin Expression Enhances IL-7 Receptor Signaling in Thymocytes during Positive Selection J. Immunol., July 1, 2007; 179(1): 126 - 131. [Abstract] [Full Text] [PDF] C. C. Tydell, E.-S. David-Fung, J. E. Moore, L. Rowen, T. Taghon, and E. V. Rothenberg Molecular Dissection of Prethymic Progenitor Entry into the T Lymphocyte Developmental Pathway J. Immunol., July 1, 2007; 179(1): 421 - 438. [Abstract] [Full Text] [PDF] J. H. Carter, J. M. Lefebvre, D. L. Wiest, and W. G. Tourtellotte Redundant Role for Early Growth Response Transcriptional Regulators in Thymocyte Differentiation and Survival J. Immunol., June 1, 2007; 178(11): 6796 - 6805. [Abstract] [Full Text] [PDF] Q. Yu and J. M. 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