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Mol Cell Biol, March 1998, p. 1248-1256, Vol. 18, No. 3
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Two Members of the Tcf Family Implicated in Wnt/beta -Catenin Signaling during Embryogenesis in the Mouse

Vladimir Korinek,1,dagger Nick Barker,1 Karl Willert,2 Miranda Molenaar,3 Jeroen Roose,1 Gerry Wagenaar,4 Marry Markman,5 Wout Lamers,5 Olivier Destree,3 and Hans Clevers1,*

Department of Immunology, University Hospital, 3508 GA Utrecht,1 Hubrecht Laboratory, Netherlands Institute for Developmental Biology,3 and Department of Hematology, University Hospital,4 3584 CX Utrecht, and Department of Anatomy and Embryology, University of Amsterdam, 1105 AZ Amsterdam,5 The Netherlands, and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-54282

Received 17 September 1997/Returned for modification 22 October 1997/Accepted 9 December 1997

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) mouse embryos but gradually disappears over the next 3 to 4 days. mTcf-4 expression occurs first at E10.5 and is restricted to di- and mesencephalon and the intestinal epithelium during embryogenesis. The mTcf-3 and mTcf-4 proteins bind a 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 stimulation and beta -catenin/Tcf transcriptional activation and imply a role for mTcf-3 and -4 in early Wnt-driven developmental decisions in the mouse embryo.

* Corresponding author. Mailing address: Department of Immunology, University Hospital Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Phone: 3130-250-7674. Fax: 3130-251-7107. E-mail: h.clevers{at}lab.azu.nl.

dagger Present address: Institute of Molecular Genetics, Videnska 1083, 142 20 Prague 4, Czech Republic.




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