在非洲爪蟾神经嵴诱导过程中,Msx1和Pax3协同介导FGF8和WNT信号。

Msx1 and Pax3 cooperate to mediate FGF8 and WNT signals during Xenopus neural crest induction.

作者信息

Monsoro-Burq Anne-Hélène, Wang Estee, Harland Richard

机构信息

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.

出版信息

Dev Cell. 2005 Feb;8(2):167-78. doi: 10.1016/j.devcel.2004.12.017.

Abstract

FGF, WNT, and BMP signaling promote neural crest formation at the neural plate boundary in vertebrate embryos. To understand how these signals are integrated, we have analyzed the role of the transcription factors Msx1 and Pax3. Using a combination of overexpression and morpholino-mediated knockdown strategies in Xenopus, we show that Msx1 and Pax3 are both required for neural crest formation, display overlapping but nonidentical activities, and that Pax3 acts downstream of Msx1. In neuralized ectoderm, Msx1 is sufficient to induce multiple early neural crest genes. Msx1 induces Pax3 and ZicR1 cell autonomously, in turn, Pax3 combined with ZicR1 activates Slug in a WNT-dependent manner. Upstream of this, WNTs initiate Slug induction through Pax3 activity, whereas FGF8 induces neural crest through both Msx1 and Pax3 activities. Thus, WNT and FGF8 signals act in parallel at the neural border and converge on Pax3 activity during neural crest induction.

摘要

成纤维细胞生长因子(FGF)、Wnt信号通路和骨形态发生蛋白(BMP)信号通路在脊椎动物胚胎的神经板边界促进神经嵴的形成。为了了解这些信号是如何整合的,我们分析了转录因子Msx1和Pax3的作用。利用非洲爪蟾中过表达和吗啉代介导的敲低策略相结合的方法,我们发现Msx1和Pax3都是神经嵴形成所必需的,表现出重叠但不完全相同的活性,并且Pax3在Msx1的下游起作用。在神经化外胚层中,Msx1足以诱导多个早期神经嵴基因。Msx1自主诱导Pax3和ZicR1,反过来,Pax3与ZicR1以Wnt依赖的方式激活Slug。在此上游,Wnt通过Pax3活性启动Slug的诱导,而FGF8通过Msx1和Pax3的活性诱导神经嵴。因此,Wnt和FGF8信号在神经边界平行作用,并在神经嵴诱导过程中汇聚于Pax3的活性。

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