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非经典Wnt信号由Kaiso转录抑制因子和p120连环蛋白调节。

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

作者信息

Kim Si Wan, Park Jae-Il, Spring Christopher M, Sater Amy K, Ji Hong, Otchere Abena A, Daniel Juliet M, McCrea Pierre D

机构信息

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, Texas 77030, USA.

出版信息

Nat Cell Biol. 2004 Dec;6(12):1212-20. doi: 10.1038/ncb1191. Epub 2004 Nov 14.

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 rearrangements. Here we demonstrate that the dual-specificity transcriptional repressor Kaiso, first identified in association with p120-catenin, 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.

摘要

原肠胚形成运动对于建立脊椎动物胚胎的三个主要胚层和基本结构至关重要。尽管所涉及的单个分子和信号通路尚不清楚,但已知非经典Wnt信号参与发育过程,包括平面细胞极性和定向细胞重排。在这里,我们证明了首先与p120连环蛋白相关联而被鉴定的双特异性转录抑制因子Kaiso,是非洲爪蟾原肠胚形成运动所必需的。此外,xKaiso的缺失导致非经典xWnt11的表达增加,这导致了xKaiso敲低表型,因为显性负性Wnt11可显著挽救该表型。我们进一步证明xWnt11是xKaiso的直接基因靶点,并且p120连环蛋白的结合在体内可解除xKaiso的抑制作用。我们的结果表明,p120连环蛋白和Kaiso是控制脊椎动物形态发生的新的发育基因调控途径的重要组成部分。

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