Article

Wnt signaling is required for thymocyte development and activates Tcf-1 mediated transcription.

Department of Immunology and Center for Biomedical Genetics, Utrecht Medical Center, Utrecht, The Netherlands.
European Journal of Immunology (Impact Factor: 4.52). 02/2001; 31(1):285-93.
Source: PubMed

ABSTRACT T cell factor / lymphocyte enhancer factor (Tcf/Lef) transcription factors complex with the transcriptional co-activator beta-catenin to transduce Wnt signals in a variety of developmental systems. The prototypic family member Tcf-1 is highly expressed in T lineage cells. Tcf1-/- mice are defective in cell cycling of early thymocyte stages. Here, we show that the interaction of beta-catenin with Tcf-1 is required for full thymocyte development. This interaction may be established by signals mediated by Wnt1 and Wnt4, leading to increased Tcf-dependent transcriptional activity in thymocytes, as demonstrated in Tcf-LacZ reporter mice. Transduction of fetal thymocytes with Wnt1 and Wnt4 results in increased survival in an in vitro cell culture system. Retroviral expression of soluble Wnt receptor mutants that block Wnt signaling inhibits thymocyte development. These results imply an important role for the Wnt cascade in thymocyte development.

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    • "OP9-DL1 stromal cells were found to express several Wnt genes, including Wnt4 and Wnt5A, and to a lesser extent, Wnt5B and Wnt10B (Fig. 5B). Of these, Wnt4 has previously been reported to have a role in thymopoiesis (Staal et al., 2001; Mulroy et al., 2002). OP9-Ctrl cells showed a similar pattern of Wnt gene expression (data not shown). "
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    • "All minimal promoters in previously generated Wnt/b-catenin signaling reporters were derived from the promoters of natural genes, such as heat shock protein, c-fos, thymidine kinase, and siamois (Riese et al., 1997; DasGupta and Fuchs, 1999; Staal et al., 2001; Dorsky et al., 2002; Geng et al., 2003; Maretto et al., 2003; Mohamed et al., 2004; Nakaya et al., 2005; Denayer et al., 2006; Moro et al., 2012). They not only contained TATA but also sequences derived from each gene promoter, which may be affected by non-specific signals (Robertson et al., 1995; Barolo, 2006). "
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