XTsh3 is an essential enhancing factor of canonical Wnt signaling in Xenopus axial determination
XTsh3 is an essential enhancing factor of canonical Wnt signaling in Xenopus axial determination
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DOI：
10.1038/sj.emboj.7601684
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发表时间：
2007-05-02
期刊：
影响因子：
11.4
通讯作者：
Sasai, Yoshiki
中科院分区：
文献类型：
--
作者：
Onai, Takayuki;Matsuo-Takasaki, Mami;Sasai, Yoshiki
在非洲爪蟾中，随着受精卵皮层旋转，Wnt活性的不对称分布导致背腹轴的建立。然而，一个清晰的DV极性是如何从Wnt活性的初始差异发展而来的仍然是难以捉摸的。我们在这里报道，teshirt类锌指因子XTsh3通过增强典型Wnt信号在背侧决定中发挥重要作用。敲除XTsh3功能会导致爪蟾胚胎的腹化。体内和体外研究表明，XTsh3以β -连环蛋白依赖的方式显著增强Wnt信号活性。当XTsh3与弱Wnt活性结合时，可协同促进腹侧次级轴的形成，而单独使用XTsh3诱导轴的能力较弱。此外，Wnt1需要XTsh3才能在体内活化。免疫染色和蛋白分析表明，XTsh3是一种与b-catenin物理结合的核蛋白，可有效提高细胞核中b-catenin的水平。我们讨论了XTsh3作为典型Wnt信号的必要扩增因子在胚胎背侧决定中的作用。
In Xenopus, an asymmetric distribution of Wnt activity that follows cortical rotation in the fertilized egg leads to the dorsal-ventral (DV) axis establishment. However, how a clear DV polarity develops from the initial difference in Wnt activity still remains elusive. We report here that the Teashirt-class Zn-finger factor XTsh3 plays an essential role in dorsal determination by enhancing canonical Wnt signaling. Knockdown of the XTsh3 function causes ventralization in the Xenopus embryo. Both in vivo and in vitro studies show that XTsh3 substantially enhances Wnt signaling activity in a beta-catenin-dependent manner. XTsh3 cooperatively promotes the formation of a secondary axis on the ventral side when combined with weak Wnt activity, whereas XTsh3 alone has little axis-inducing ability. Furthermore, Wnt1 requires XTsh3 for its dorsalizing activity in vivo. Immunostaining and protein analyses indicate that XTsh3 is a nuclear protein that physically associates with b-catenin and efficiently increases the level of b-catenin in the nucleus. We discuss the role of XTsh3 as an essential amplifying factor of canonical Wnt signaling in embryonic dorsal determination.