Axud1 Integrates Wnt Signaling and Transcriptional Inputs to Drive Neural Crest Formation.
Axud1 Integrates Wnt Signaling and Transcriptional Inputs to Drive Neural Crest Formation.
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DOI：
10.1016/j.devcel.2015.06.024
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发表时间：
2015-09-14
影响因子：
11.8
通讯作者：
Bronner ME
中科院分区：
文献类型：
--
作者：
Simões-Costa M;Stone M;Bronner ME
神经嵴细胞是由转录因子和信号分子共同作用在神经板边缘诱导形成的。本研究表明，作为Wnt信号的下游效应因子，Axud1是整合信号和转录信号介导神经嵴形成的关键缺失环节。Axud1是一种在神经嵴祖细胞中以Wnt1/β-catenin依赖方式表达的转录因子。Axud1缺失导致与神经嵴规范相关的多个基因下调，类似于Wnt1敲低的影响。重要的是，在Wnt信号中断后，Axud1足以挽救神经嵴的形成。此外，它在体内与神经板边界基因Pax7和Msx1物理相互作用，直接激活干细胞因子FoxD3的转录，启动神经嵴程序。因此，Axud1将Wnt信号与转录输入相结合，赋予神经嵴独特的分子特征。
Neural crest cells are induced at the neural plate border by the combined action of transcription factors and signaling molecules. Here, we show that Axud1, a downstream effector of Wnt signaling, represents a critical missing link that integrates signaling and transcriptional cues to mediate neural crest formation. Axud1 is a transcription factor expressed in neural crest progenitors in a Wnt1/β-catenin dependent manner. Axud1 loss leads to downregulation of multiple genes involved in neural crest specification, similar to the effects of Wnt1 knockdown. Importantly, Axud1 is sufficient to rescue neural crest formation after disruption of Wnt signaling. Furthermore, it physically interacts with neural plate border genes Pax7 and Msx1 in vivo to directly activate transcription of stem cell factor FoxD3, initiating the neural crest program. Thus, Axud1 integrates Wnt signaling with transcriptional inputs to endow the neural crest with its unique molecular signature.