title: Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse.
abstract: 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.
authors.affiliation: Department of Immunology, University Hospital, Utrecht, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Korinek
authors.forename: N
authors.initials: N
authors.lastname: Barker
authors.forename: K
authors.initials: K
authors.lastname: Willert
authors.forename: M
authors.initials: M
authors.lastname: Molenaar
authors.forename: J
authors.initials: J
authors.lastname: Roose
authors.forename: G
authors.initials: G
authors.lastname: Wagenaar
authors.forename: M
authors.initials: M
authors.lastname: Markman
authors.forename: W
authors.initials: W
authors.lastname: Lamers
authors.forename: O
authors.initials: O
authors.lastname: Destree
authors.forename: H
authors.initials: H
authors.lastname: Clevers
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D015870:Gene Expression; D017930:Genes, Reporter; D024002:HMGB Proteins; D006801:Humans; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D015533:Transcriptional Activation; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D024002:HMGB Proteins; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; C544894:TCF7L2 protein, human; C544913:Tcf7l1 protein, mouse; C553060:Tcf7l1 protein, rat; C544895:Tcf7l2 protein, mouse; C553059:Tcf7l2 protein, rat; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C495245:Wnt1 protein, rat; D029961:Zebrafish Proteins; D051176:beta Catenin; D008156:Luciferases