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

Author:

Korinek Vladimir1,Barker Nick1,Willert Karl2,Molenaar Miranda3,Roose Jeroen1,Wagenaar Gerry4,Markman Marry5,Lamers Wout5,Destree Olivier3,Clevers Hans1

Affiliation:

1. Department of Immunology, University Hospital, 3508 GA Utrecht,1

2. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305-54282

3. Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3 and

4. Department of Hematology, University Hospital, 4 3584 CX Utrecht, and

5. Department of Anatomy and Embryology, University of Amsterdam, 1105 AZ Amsterdam, 5 The Netherlands, and

Abstract

ABSTRACT Tcf transcription factors interact with β-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 β-catenin. Overexpression of Wnt-1 in a mammary epithelial cell line leads to the formation of a nuclear complex between β-catenin and Tcf proteins and to Tcf reporter gene transcription. These data demonstrate a direct link between Wnt stimulation and β-catenin/Tcf transcriptional activation and imply a role for mTcf-3 and -4 in early Wnt-driven developmental decisions in the mouse embryo.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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