2 MEMBERS OF THE TCF FAMILY IMPLICATED IN WNT BETA-CATENIN SIGNALING DURING EMBRYOGENESIS IN THE MOUSE/

Tcf transcription factors interact with beta-catenin and Armadillo to mediate Wnt/Wingless signaling. We now report the characterization of genes encoding two murine members of the Tcf family, mTcf-3 and mTCf-4 . mTCf-3 mRNA is ubiquitously present in embryonic day 6.5 (E6.5) mous e embryos but gradually disappears over the next 3 to 4 days. mTcf-4 e xpression occurs first at E10.5 and is restricted to di-and mesencepha lon and the intestinal epithelium during embryogenesis. The mTcf-3 and mTcf-4 proteins bind ii canonical Tcf DNA motif and can complex with the transcriptional coactivator beta-catenin. Overexpression of Wnt-1 in a mammary epithelial cell line leads to the formation of a nuclear complex between beta-catenin and Tcf proteins and to Tcf reporter gene transcription. These data demonstrate a direct link between Wnt stimu lation and beta-catenin/Tcf transcriptional activation and imply a rol e for mTcf-3 and -4 in early Wnt driven developmental decisions in the mouse embryo.