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Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin


Gastrulation movements are critical for establishing the three principal germ layers and the basic architecture of vertebrate embryos. Although the individual molecules and pathways involved are not clearly understood, non-canonical Wnt signals are known to participate in developmental processes, including planar cell polarity and directed cell rearrangements1,2. Here we demonstrate that the dual-specificity transcriptional repressor Kaiso3,4,5, first identified in association with p120-catenin6,7, is required for Xenopus gastrulation movements. In addition, depletion of xKaiso results in increased expression of the non-canonical xWnt11, which contributes to the xKaiso knockdown phenotype as it is significantly rescued by dominant-negative Wnt11. We further demonstrate that xWnt11 is a direct gene target of xKaiso and that p120-catenin association relieves xKaiso repression in vivo. Our results indicate that p120-catenin and Kaiso are essential components of a new developmental gene regulatory pathway that controls vertebrate morphogenesis.

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Figure 1: xKaiso-depleted or over-expressing Xenopus embryos exhibit gastrulation defects.
Figure 2: xKaiso is required for the morphogenetic movements of convergent extension.
Figure 3: The non-canonical xWnt11 contributes to the xKaiso-depletion phenotype and is a direct Kaiso gene target.
Figure 4: xWnt11 gene activity is sensitive to xKaiso levels.
Figure 5: p120-catenin relieves xKaiso repression of the Wnt11 gene.

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  1. Wallingford, J. B., Fraser, S. E. & Harland, R. M. Convergent extension: the molecular control of polarized cell movement during embryonic development. Dev. Cell 2, 695–706 (2002).

    Article  CAS  Google Scholar 

  2. Mlodzik, M. Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation? Trends Genet. 18, 564–571 (2002).

    Article  CAS  Google Scholar 

  3. Prokhortchouk, A. et al. The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor. Genes Dev. 15, 1613–1618 (2001).

    Article  CAS  Google Scholar 

  4. Daniel, J. M., Spring, C. M., Crawford, H. C., Reynolds, A. B. & Baig, A. The p120ctn-binding partner Kaiso is a bi-modal DNA-binding protein that recognizes both a sequence-specific consensus and methylated CpG dinucleotides. Nucleic Acids Res. 30, 2911–2919 (2002).

    Article  CAS  Google Scholar 

  5. Yoon, H. G., Chan, D. W., Reynolds, A. B., Qin, J. & Wong, J. N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso. Mol. Cell 12, 723–734 (2003).

    Article  CAS  Google Scholar 

  6. Daniel, J. M. & Reynolds, A. B. The catenin p120ctn interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. Mol. Cell. Biol. 19, 3614–3623 (1999).

    Article  CAS  Google Scholar 

  7. Kim, S. W. et al. Isolation and characterization of XKaiso, a transcriptional repressor that associates with the catenin Xp120ctn in Xenopus laevis. J. Biol. Chem. 277, 8202–8208 (2002).

    Article  CAS  Google Scholar 

  8. Anastasiadis, P. Z. & Reynolds, A. B. The p120 catenin family: complex roles in adhesion, signaling and cancer. J. Cell Sci. 113, 1319–1334 (2000).

    CAS  PubMed  Google Scholar 

  9. Nelson, W. J. & Nusse, R. Convergence of Wnt, β-catenin, and cadherin pathways. Science 303, 1483–1487 (2004).

    Article  CAS  Google Scholar 

  10. van Noort, M. & Clevers, H. TCF transcription factors, mediators of Wnt-signaling in development and cancer. Dev. Biol. 244, 1–8 (2002).

    Article  CAS  Google Scholar 

  11. Anastasiadis, P. Z. & Reynolds, A. B. Regulation of Rho GTPases by p120-catenin. Curr. Opin. Cell Biol. 13, 604–610 (2001).

    Article  CAS  Google Scholar 

  12. Fang, X. et al. Vertebrate development requires ARVCF and p120 catenin and their interplay with RhoA and Rac. J. Cell Biol. 165, 87–98 (2004).

    Article  CAS  Google Scholar 

  13. Chen, X., Kojima, S., Borisy, G. G. & Green, K. J. p120 catenin associates with kinesin and facilitates the transport of cadherin–catenin complexes to intercellular junctions. J. Cell Biol. 163, 547–557 (2003).

    Article  CAS  Google Scholar 

  14. Franz, C. M. & Ridley, A. J. p120 Catenin associates with microtubules: Inverse relationship between microtubule binding and Rho GTPase regulation. J. Biol. Chem. 279, 6588–6594 (2004).

    Article  CAS  Google Scholar 

  15. Paulson, A. F., Fang, X., Ji, H., Reynolds, A. B. & McCrea, P. D. Misexpression of the catenin p120ctn1A perturbs Xenopus gastrulation but does not elicit Wnt-directed axis specification. Dev. Biol. 207, 350–363 (1999).

    Article  CAS  Google Scholar 

  16. Geis, K., Aberle, H., Kuhl, M., Kemler, R. & Wedlich, D. Expression of the Armadillo family member p120cas1B in Xenopus embryos affects head differentiation but not axis formation. Dev. Genes Evol. 207, 471–481 (1998).

    Article  CAS  Google Scholar 

  17. Thoreson, M. A. & Reynolds, A. B. Altered expression of the catenin p120 in human cancer: implications for tumor progression. Differentiation 70, 583–589 (2002).

    Article  CAS  Google Scholar 

  18. Heasman, J. Morpholino oligos: making sense of antisense? Dev. Biol. 243, 209–214 (2002).

    Article  CAS  Google Scholar 

  19. Gumbiner, B. M. Regulation of cadherin adhesive activity. J. Cell Biol. 148, 399–404 (2000).

    Article  CAS  Google Scholar 

  20. Keller, R. Shaping the vertebrate body plan by polarized embryonic cell movements. Science 298, 1950–1954 (2002).

    Article  CAS  Google Scholar 

  21. Keller, R. & Danilchik, M. Regional expression, pattern and timing of convergence and extension during gastrulation of Xenopus laevis. Development 103, 193–209 (1988).

    CAS  PubMed  Google Scholar 

  22. Smith, J. C., Conlon, F. L., Saka, Y. & Tada, M. Xwnt11 and the regulation of gastrulation in Xenopus. Philos. Trans R. Soc. Lond. B. Biol. Sci. 355, 923–930 (2000).

    Article  CAS  Google Scholar 

  23. Tada, M. & Smith, J. C. Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway. Development 127, 2227–2238 (2000).

    CAS  PubMed  Google Scholar 

  24. Rothbacher, U. et al. Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. EMBO J. 19, 1010–1022 (2000).

    Article  CAS  Google Scholar 

  25. Habas, R., Dawid, I. B. & He, X. Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation. Genes Dev. 17, 295–309 (2003).

    Article  CAS  Google Scholar 

  26. Kelly, K. F., Spring, C. M., Otchere, A. A. & Daniel, J. M. NLS-dependent nuclear localization of p120ctn is necessary to relieve Kaiso-mediated transcriptional repression. J. Cell Sci. 117, 2675–2686 (2004).

    Article  CAS  Google Scholar 

  27. Eisenberg, C. A., Gourdie, R. G. & Eisenberg, L. M. Wnt-11 is expressed in early avian mesoderm and required for the differentiation of the quail mesoderm cell line QCE-6. Development 124, 525–536 (1997).

    CAS  PubMed  Google Scholar 

  28. Medina, A., Reintsch, W. & Steinbeisser, H. Xenopus frizzled 7 can act in canonical and non-canonical Wnt signaling pathways: implications on early patterning and morphogenesis. Mech. Dev. 92, 227–237 (2000).

    Article  CAS  Google Scholar 

  29. Strutt, H., Cavalli, G. & Paro, R. Co-localization of Polycomb protein and GAGA factor on regulatory elements responsible for the maintenance of homeotic gene expression. EMBO J. 16, 3621–3632 (1997).

    Article  CAS  Google Scholar 

  30. Sater, A. K., Steinhardt, R. A. & Keller, R. Induction of neuronal differentiation by planar signals in Xenopus embryos. Dev. Dyn. 197, 268–80 (1993).

    Article  CAS  Google Scholar 

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We thank B. M. Gumbiner for the anti-E-cadherin antibody; R. Keller for xWnt11 and dnxWnt11 plasmids; J. B. Wallingford and R. M. Harland for xDsh constructs; and L. Etkin, M. Jamrich and members of the McCrea laboratory for critical reading of the manuscript. This work was supported by National Institutes of Health grant RO1 (GM52112) and an Institutional Research Grant to P.D.M., as well as a grant from the Canadian Institutes of Health Research (MOP 42045) to J.M.D. DNA sequencing and other core facilities were supported by the University of Texas M.D. Anderson Cancer Center NCI Core Grant CA-16672.

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Kim, S., Park, JI., Spring, C. et al. Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin. Nat Cell Biol 6, 1212–1220 (2004).

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