XTcf-3 Transcription Factor Mediates β-Catenin-Induced Axis Formation in Xenopus Embryos
Open accessAbstract
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 beta-catenin. Microinjection of XTcf-3 mRNA in embryos results in nuclear translocation of beta-catenin. The beta-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 (delta N) abrogates the interaction with beta-catenin, as well as the consequent transcription activation. This dominant-negative delta N mutant suppresses the induction of axis duplication by microinjected beta-catenin. It also suppresses endogenous axis specification upon injection into the dorsal blastomeres of a 4-cell-stage embryo. We propose that signaling by beta-catenin involves complex formation with XTcf-3, followed by nuclear translocation and activation of specific XTcf-3 target genes.
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LEF-1/TCF family members share overall sequence similarity.
“Although LEF-1/TCF family members share overall sequence similarity, these two regions are particularly conserved (18).”
LEF-1/TCF forms a complex with β-catenin in response to Wnt stimulation.
“LEF-1/TCF has been shown to form a complex with β-catenin in response to Wnt stimulation (2, 4, 18, 34).”
The NH2-terminal β-catenin-binding and COOH-terminal HMG DNA-binding regions of LEF-1/TCF are particularly conserved.
“Although LEF-1/TCF family members share overall sequence similarity, these two regions are particularly conserved (18).”
The β-catenin-LEF-1/TCF complex activates Wnt target genes in the nucleus.
“The β-catenin-LEF-1/TCF complex, in turn, activates Wnt target genes in the nucleus (2, 4, 18, 34).”
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- Authors
- Molenaar, M., van de Wetering, M., Oosterwegel, M., Peterson-Maduro, J., Godsave, S., Korinek, V., Roose, J., Destrée, O., & Clevers, H.
- Affiliations
- University Medical Center Utrecht (NL)
- Hubrecht Institute for Developmental Biology and Stem Cell Research (NL)
- Corresponding author
- Clevers, Hans
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1996-08
- Volume
- 86
- Issue
- 3
- Pages
- 391-399
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2090636859
- Cited by
- 1,824
- References
- 0
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 23 · 2023: 33 · 2022: 42 · 2021: 54 · 2020: 39 · 2019: 34 · 2018: 45 · 2017: 50 · 2016: 45 · 2015: 41 · 2014: 67 · 2013: 55 · 2012: 57
- FWCI
- 42.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion, other-oa)
- Funders
- ACT Government
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- β-catenin, Wnt signaling, axis formation, axis duplication, HMG-box transcription factor, nuclear translocation, transcriptional activation, dominant-negative mutant, Xenopus embryo, TCF1, LEF1
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cytoskeletal Proteins, Embryonic Induction, Molecular Sequence Data, Morphogenesis, Transcription Factors, Transcription, Genetic, Xenopus, Restriction Mapping, Trans-Activators, Mutagenesis, Site-Directed, DNA, Complementary, Gene Expression Regulation, Developmental, HMGB Proteins, Xenopus Proteins, beta Catenin, TCF Transcription Factors, Transcription Factor 7-Like 1 Protein, Transcription Factor 3
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