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BMP 信号在中脑神经嵴细胞分层过程中的基本功能和靶标。

Essential function and targets of BMP signaling during midbrain neural crest delamination.

机构信息

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.

出版信息

Dev Biol. 2021 Sep;477:251-261. doi: 10.1016/j.ydbio.2021.06.003. Epub 2021 Jun 6.

Abstract

BMP signaling plays iterative roles during vertebrate neural crest development from induction through craniofacial morphogenesis. However, far less is known about the role of BMP activity in cranial neural crest epithelial-to-mesenchymal transition and delamination. By measuring canonical BMP signaling activity as a function of time from specification through early migration of avian midbrain neural crest cells, we found elevated BMP signaling during delamination stages. Moreover, inhibition of canonical BMP activity via a dominant negative mutant Type I BMP receptor showed that BMP signaling is required for neural crest migration from the midbrain, independent from an effect on EMT and delamination. Transcriptome profiling on control compared to BMP-inhibited cranial neural crest cells identified novel BMP targets during neural crest delamination and early migration including targets of the Notch pathway that are upregulated following BMP inhibition. These results suggest potential crosstalk between the BMP and Notch pathways in early migrating cranial neural crest and provide novel insight into mechanisms regulated by BMP signaling during early craniofacial development.

摘要

BMP 信号在脊椎动物神经嵴发育过程中发挥迭代作用,从诱导到颅面形态发生。然而,关于 BMP 活性在颅神经嵴上皮-间充质转化和分层中的作用知之甚少。通过测量从中胚层神经嵴细胞的指定到早期迁移的时间的规范 BMP 信号活性的函数,我们发现分层阶段 BMP 信号升高。此外,通过显性负突变型 I 型 BMP 受体抑制规范 BMP 活性表明 BMP 信号对于从中脑迁移的神经嵴是必需的,与 EMT 和分层的影响无关。与 BMP 抑制的颅神经嵴细胞相比,对对照的转录组谱分析在神经嵴分层和早期迁移过程中确定了新的 BMP 靶标,包括 Notch 途径的靶标,其在 BMP 抑制后上调。这些结果表明在早期迁移的颅神经嵴中 BMP 和 Notch 途径之间存在潜在的串扰,并为 BMP 信号在早期颅面发育过程中的调节机制提供了新的见解。

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