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

Nature Cell Biology volume 6, pages 1212–1220 (2004)Cite this article

Abstract

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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Acknowledgements

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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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, The University of Texas Graduate School of Biomedical Science, Houston, 77030, Texas, USA

    Si Wan Kim, Jae-Il Park, Hong Ji & Pierre D. McCrea

  2. Program in Genes and Development, The University of Texas M.D. Anderson Cancer Center, The University of Texas Graduate School of Biomedical Science, Houston, 77030, Texas, USA

    Jae-Il Park & Pierre D. McCrea

  3. Department of Biology, McMaster University, Hamilton, L8S 4K1, Ontario, Canada

    Christopher M. Spring, Abena A. Otchere & Juliet M. Daniel

  4. Department of Biology, University of Houston, Houston, 77204, Texas, USA

    Amy K. Sater

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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). https://doi.org/10.1038/ncb1191

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