XTcf-3 Transcription Factor Mediates β-Catenin-Induced Axis Formation in Xenopus Embryos

• Published in: Cell 1996-08, Vol.86 (3), p.391-399
• Main Authors: Molenaar, Miranda, van de Wetering, Marc, Oosterwegel, Mariette, Peterson-Maduro, Josi, Godsave, Susan, Korinek, Vladimir, Roose, Jeroen, Destrée, Olivier, Clevers, Hans
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; beta Catenin; Cytoskeletal Proteins - physiology; DNA, Complementary; Embryonic Induction; Freshwater; Gene Expression Regulation, Developmental; HMGB Proteins; Molecular Sequence Data; Morphogenesis - genetics; Morphogenesis - physiology; Mutagenesis, Site-Directed; Restriction Mapping; TCF Transcription Factors; Trans-Activators; Transcription Factor 3; Transcription Factor 7-Like 1 Protein; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Xenopus; Xenopus Proteins
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80112-9

XTcf-3 is a maternally expressed Xenopus homolog of the mammalian HMG box factors Tcf-1 and Lef-1. The N-terminus of XTcf-3 binds to β-catenin. Microinjection of XTcf-3 mRNA in embryos results in nuclear translocation of β-catenin. The β-catenin–XTcf-3 complex activates transcription in a transient reporter gene assay, while XTcf-3 by itself is silent. N-terminal deletion of XTcf-3 (ΔN) abrogates the interaction with β-catenin, as well as the consequent transcription activation. This dominant-negative ΔN mutant suppresses the induction of axis duplication by microinjected β-catenin. It also suppresses endogenous axis specification upon injection into the dorsal blastomeres of a 4-cell-stage embryo. We propose that signaling by β-catenin involves complex formation with XTcf-3, followed by nuclear translocation and activation of specific XTcf-3 target genes.