Mechanism of fore-mid-brain determination by XSa1F

本研究的目的是了解早期脊椎动物胚胎的分子机制，特别是在神经系统中，通过集中在爪蟾吻侧神经外胚层发育中的锌指蛋白及其相关分子的作用。我们以前已经分离出锌指因子XSa 1F，它在确定喙脑中起着至关重要的作用。在这项研究中，我们确定了另一个锌指转录因子，XTsh 3，这是在非洲爪蟾尾神经系统中表达。我们发现，XTsh 3是尾神经组织正常发育所需的促进因子。XTsh 3的过表达引起神经组织的尾状化，并抑制前脑发育。相反，XTsh 3-MO注射，阻断其功能，促进前脑发育。在信号转导分析中，我们发现XTsh 3增强Wnt/b-catenin信号转导。XTsh 3与b-连环蛋白和Tcf 3结合，并放大Wnt诱导的转录。与这些观察结果一致，XTsh 3-MO注射到中内胚层组织抑制背侧发育，导致整个胚胎的强烈腹侧化。因此，除了XSa 1F作为Wnt信号传导的负调节剂外，XTsh 3在Wnt通路的精细调节中发挥重要作用。XSa 1F和XTsh 3的拮抗对可能充当Wnt-On与-Wnt的二元开关系统。违反规定。

The aim of this study is to understand molecular mechanisms of the early vertebrate embryo, particularly in the nervous system, by focusing on the roles of zinc-finger proteins and their related molecules in the rostral neuroectodermal development of Xenopus. We had previously isolated the zinc-finger factor XSa1F, which plays an essential role in the determination of the rostral brain. In this study, we identified another zinc-finger transcription factor, XTsh3, which is expressed in the Xenopus caudal nervous system. We showed that XTsh3 is a promoting factor required for the proper development of the caudal neural tissues. Overexpression of XTsh3 caused caudalization of the neural tissues and suppressed forebrain development. Conversely, XTsh3-MO injection, which blocks its function, enhanced forebrain development. In signaling analysis, we found that XTsh3 augments Wnt/b-catenin signaling. XTsh3 binds to both b-catenin and Tcf3, and amplifies Wnt-induced transcription. Consistent with these observations, XTsh3-MO injection into mesoendodermal tissues inhibited dorsal development, leading to strong ventralization of the whole embryo. Thus, in addition to XSa1F, which acts as a negative modulator of Wnt signaling, XTsh3 plays an important role in the fine modulation of the Wnt pathway. The antagonistic pair of XSa1F and XTsh3 is likely to function as a binary switching system of Wnt-On vs.-Off regulations.