Xenopus Nkx6.3 is a neural plate border specifier required for neural crest development.

Xenopus Nkx6.3 is a neural plate border specifier required for neural crest development.
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Xenopus nkx6.3 是神经嵴发育所需的神经板边界指定器。

DOI:
10.1371/journal.pone.0115165
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Mao B
Mao B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang Z;Shi Y;Zhao S;Li J;Li C;Mao B

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在脊椎动物中,神经板边界(NPB)是由一组转录因子包括Dlx3,Msx1和Zic1建立的。这些NPB指定符之间的串扰支配NPB区域分离成基板和神经嵴(NC)领土,以及它们的进一步分化。了解NPB形成和NC发展的机制对于我们了解相关的人类疾病至关重要。在这里,我们鉴定了Nkx家族的转录因子Nkx6.3,作为非洲爪蟾胚胎神经嵴发育所需的新NPB指定因子。XNkx6.3在神经胚阶段的神经板边缘区域的外胚层中表达,覆盖表皮、基板和神经嵴区域,但不覆盖神经板。显性负性结构或特异性吗啉代抑制Nkx6.3导致神经嵴缺陷,而Nkx6.3过表达诱导前神经褶中的异位神经嵴。在动物帽中,Nkx6.3单独能够启动整个神经嵴调节网络,并稳健地诱导神经嵴命运。我们发现Nkx6.3的过表达影响多种信号通路,创造了神经嵴发育所需的高Wnt,低BMP环境。Nkx6.3功能的获得和丧失对已知NPB基因的表达具有复合作用,这与Dlx3的作用在很大程度上相反。Dlx3的过表达阻断Nkx6.3的NC诱导活性。Nkx6.3,Dlx3和Msx1之间的串扰可能是至关重要的适当NPB的形成和神经嵴的发展在非洲爪蟾。
In vertebrates, the neural plate border (NPB) is established by a group of transcription factors including Dlx3, Msx1 and Zic1. The crosstalk between these NPB specifiers governs the separation of the NPB region into placode and neural crest (NC) territories and also their further differentiation. Understanding the mechanisms of NPB formation and NC development is critical for our knowledge of related human diseases. Here we identified Nkx6.3, a transcription factor of the Nkx family, as a new NPB specifier required for neural crest development in Xenopus embryos. XNkx6.3 is expressed in the ectoderm of the neural plate border region at neurula stages, covering the epidermis, placode and neural crest territories, but not the neural plate. Inhibition of Nkx6.3 by dominant negative construct or specific morpholino leads to neural crest defects, while overexpression of Nkx6.3 induces ectopic neural crest in the anterior neural fold. In animal caps, Nkx6.3 alone is able to initiate the whole neural crest regulatory network and induces neural crest fate robustly. We showed that overexpression of Nkx6.3 affects multiple signaling pathways, creating a high-Wnt, low-BMP environment required for neural crest development. Gain- and loss-of-function of Nkx6.3 have compound effects on the expression of known NPB genes, which is largely opposite to that of Dlx3. Overexpression of Dlx3 blocks the NC inducing activity of Nkx6.3. The crosstalk between Nkx6.3, Dlx3 and Msx1 is likely crucial for proper NPB formation and neural crest development in Xenopus.
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