Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway
Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway
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DOI：
10.1016/j.ydbio.2011.10.026
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发表时间：
2012-01-15
影响因子：
2.7
通讯作者：
Aruga, Jun
中科院分区：
文献类型：
--
作者：
Fujimi, Takahiko J.;Hatayama, Minoru;Aruga, Jun
Zic 3控制非洲爪蟾胚胎的神经外胚层分化和左右图案化。在这里，我们证明了Zic 3可以抑制Wnt/β-连环蛋白信号传导，并控制脊索和Spemann组织者的发育。当我们通过将其RNA注射到2细胞期胚胎的背侧边缘区来过表达Zic 3时，胚胎失去了中胚层背中线结构，并且显示出组织者标记物（Siamois和Goosecoid）和脊索标记物（Xnot）的表达减少。Siamois RNA的共注射部分地挽救了由Zic 3过表达引起的Xnot表达的减少。由于Siamois在组织者区域中的表达受Wnt/β-连环蛋白信号传导控制，我们随后检查了Zic 3和Wnt信号传导之间的功能相互作用。共注射非洲爪蟾Zic RNA和β-连环蛋白RNA与对Wnt/β-连环蛋白级联反应的报告基因表明，Zic 1、Zic 2、Zic 3、Zic 4和Zic 5都可以抑制β-连环蛋白介导的转录激活。此外，共注射Zic 3 RNA抑制了爪蟾胚胎腹侧注射β-连环蛋白RNA引起的次级轴形成。Zic 3介导的Wnt/β-catenin信号抑制需要Zic 3的核定位，并涉及β-catenin核转运的减少和β-catenin降解的增强。此外。Zic 3与Tcf 1 α（β-连环蛋白辅因子）和XIC（含I-mfa结构域的背前发育所需因子）共沉淀。本报告中的发现产生了一种新的Wnt/β-连环蛋白信号转导微调系统。(C)2011 Elsevier Inc. All rights reserved.
Zic3 controls neuroectodermal differentiation and left-right patterning in Xenopus laevis embryos. Here we demonstrate that Zic3 can suppress Wnt/beta-catenin signaling and control development of the notochord and Spemann's organizer. When we overexpressed Zic3 by injecting its RNA into the dorsal marginal zone of 2-cell-stage embryos, the embryos lost mesodermal dorsal midline structures and showed reduced expression of organizer markers (Siamois and Goosecoid) and a notochord marker (Xnot). Co-injection of Siamois RNA partially rescued the reduction of Xnot expression caused by Zic3 overexpression. Because the expression of Siamois in the organizer region is controlled by Wnt/beta-catenin signaling, we subsequently examined the functional interaction between Zic3 and Wnt signaling. Co-injection of Xenopus Zic RNAs and beta-catenin RNA with a reporter responsive to the Wnt/beta-catenin cascade indicated that Zic1, Zic2, Zic3, Zic4, and Zic5 can all suppress beta-catenin-mediated transcriptional activation. In addition, co-injection of Zic3 RNA inhibited the secondary axis formation caused by ventral-side injection of beta-catenin RNA in Xenopus embryos. Zic3-mediated Wnt/beta-catenin signal suppression required the nuclear localization of Zic3, and involved the reduction of beta-catenin nuclear transport and enhancement of beta-catenin degradation. Furthermore. Zic3 co-precipitated with Tcf1 (a (beta-catenin co-factor) and XIC (I-mfa domain containing factor required for dorsoanterior development). The findings in this report produce a novel system for fine-tuning of Wnt/beta-catenin signaling. (C) 2011 Elsevier Inc. All rights reserved.