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

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.

[1]  P. McCrea,et al.  Overexpression of cadherins and underexpression of β-catenin inhibit dorsal mesoderm induction in early Xenopus embryos , 1994, Cell.

[2]  H. Clevers,et al.  Sox‐4, an Sry‐like HMG box protein, is a transcriptional activator in lymphocytes. , 1993, The EMBO journal.

[3]  H C Clevers,et al.  A common ancestor of the mammalian transcription factors TCF‐1 and TCF‐1α/LEF‐1 expressed in chicken T cells , 1992, European journal of immunology.

[4]  P. Lemaire,et al.  Expression cloning of Siamois, a xenopus homeobox gene expressed in dorsal-vegetal cells of blastulae and able to induce a complete secondary axis , 1995, Cell.

[5]  R. Kemler,et al.  The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. , 1989, The EMBO journal.

[6]  Hans Clevers,et al.  An HMG-box-containing T-cell factor required for thymocyte differentiation , 1995, Nature.

[7]  W. Baarends,et al.  Characterization of a functional promoter for the Xenopus wnt-1 gene on vivo. , 1994, Oncogene.

[8]  P. McCrea,et al.  Induction of a secondary body axis in Xenopus by antibodies to beta- catenin , 1993, The Journal of cell biology.

[9]  S. Friend,et al.  Structure and expression of the Xenopus retinoblastoma gene. , 1992, Developmental biology.

[10]  G. Veenstra,et al.  Whole-mount immunohistochemistry on Xenopus embryos using far-red fluorescent dyes. , 1995, Trends in genetics : TIG.

[11]  M. Takeichi,et al.  Transmembrane control of cadherin-mediated cell-cell adhesion. , 1993, Seminars in cell biology.

[12]  Sven Berg,et al.  A repeating amino acid motif shared by proteins with diverse cellular roles , 1994, Cell.

[13]  H Clevers,et al.  Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties , 1996, Molecular and cellular biology.

[14]  H. Clevers,et al.  Cloning of murine TCF-1, a T cell-specific trans cription factor interacting with functional motifs in the CD3ε and T cell receptor α enhancers. , 1991 .

[15]  Gert Jan C. Veenstra,et al.  Dynamic and differential Oct-1 expression during early Xenopus embryogenesis: persistence of Oct-1 protein following down-regulation of the RNA , 1995, Mechanisms of Development.

[16]  R. Grosschedl,et al.  LEF‐1 contains an activation domain that stimulates transcription only in a specific context of factor‐binding sites. , 1993, The EMBO journal.

[17]  I Fariñas,et al.  Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. , 1994, Genes & development.

[18]  N. Perrimon,et al.  Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled. , 1995, Development.

[19]  H Clevers,et al.  Cloning of murine TCF-1, a T cell-specific transcription factor interacting with functional motifs in the CD3-epsilon and T cell receptor alpha enhancers , 1991, The Journal of experimental medicine.

[20]  D. Melton,et al.  Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction. , 1987, Development.

[21]  N. Perrimon,et al.  Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled. , 1995, Development.

[22]  K. Jones,et al.  The hLEF/TCF-1 alpha HMG protein contains a context-dependent transcriptional activation domain that induces the TCR alpha enhancer in T cells. , 1993, Genes & development.

[23]  W. Birchmeier,et al.  E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton , 1994, The Journal of cell biology.

[24]  T. Watabe,et al.  Molecular mechanisms of Spemann's organizer formation: conserved growth factor synergy between Xenopus and mouse. , 1995, Genes & development.

[25]  Danica Zivkovic,et al.  Regulation of the zebrafish goosecoid promoter by mesoderm inducing factors and Xwnt1 , 1996, Mechanisms of Development.

[26]  H Clevers,et al.  A gene family of HMG-box transcription factors with homology to TCF-1. , 1992, Nucleic acids research.

[27]  Norbert Perrimon,et al.  dishevelled and armadillo act in the Wingless signalling pathway in Drosophila , 1994, Nature.

[28]  Harold E. Varmus,et al.  Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos , 1995, Nature.

[29]  H Clevers,et al.  Differential expression of the HMG box factors TCF-1 and LEF-1 during murine embryogenesis. , 1993, Development.

[30]  K. Kao,et al.  The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos. , 1988, Developmental biology.

[31]  R. Harland,et al.  In situ hybridization: an improved whole-mount method for Xenopus embryos. , 1991, Methods in cell biology.

[32]  K. Jones,et al.  A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer. , 1991, Genes & development.

[33]  William C. Smith,et al.  Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos , 1992, Cell.

[34]  R Grosschedl,et al.  LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected]. , 1991, Genes & development.

[35]  Jane A. Langdale,et al.  In situ Hybridization , 1994 .

[36]  H. Clevers,et al.  Identification and cloning of TCF‐1, a T lymphocyte‐specific transcription factor containing a sequence‐specific HMG box. , 1991, The EMBO journal.

[37]  Andrew P. McMahon,et al.  Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis , 1989, Cell.

[38]  E. Wieschaus,et al.  The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties , 1992, The Journal of cell biology.

[39]  Jan Castrop,et al.  A gene family of HMG box factors with homology to TCF-1 , 1992 .

[40]  P. McCrea,et al.  Embryonic axis induction by the armadillo repeat domain of beta- catenin: evidence for intracellular signaling , 1995, The Journal of cell biology.

[41]  E. Wieschaus,et al.  The segment polarity gene armadillo interacts with the wingless signaling pathway in both embryonic and adult pattern formation. , 1991, Development.

[42]  Ken W. Y. Cho,et al.  Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid , 1991, Cell.

[43]  H Clevers,et al.  The human TCF-1 gene encodes a nuclear DNA-binding protein uniquely expressed in normal and neoplastic T-lineage lymphocytes. , 1995, Blood.

[44]  C W Turck,et al.  A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. , 1991, Science.

[45]  M. Takeichi,et al.  Transmembrane control of cadherin-mediated cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin. , 1989, Cell regulation.

[46]  M. Waterman,et al.  The Nuclear Localization Signal of Lymphoid Enhancer Factor-1 Is Recognized by Two Differentially Expressed Srp1-Nuclear Localization Sequence Receptor Proteins (*) , 1996, The Journal of Biological Chemistry.