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

Essential function and targets of BMP signaling during midbrain neural crest delamination.
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DOI:
10.1016/j.ydbio.2021.06.003
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发表时间:
2021-09
影响因子:
2.7
通讯作者:
Bronner ME
Bronner ME
中科院分区:
生物学3区
文献类型:
--
作者:
Piacentino ML;Hutchins EJ;Bronner ME

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BMP信号在脊椎动物神经嵴从诱导到颅面形态发生的发育过程中起着反复的作用。然而,BMP活性在颅神经嵴上皮向间充质转化和分层中的作用知之甚少。通过测量典型的BMP信号活性作为时间的函数,从规范通过早期迁移的鸟类中脑神经嵴细胞,我们发现升高的BMP信号在分层阶段。此外,通过显性失活突变I型BMP受体抑制典型BMP活性表明,BMP信号传导是从中脑神经嵴迁移所需的,独立于对EMT和分层的影响。与BMP抑制的颅神经嵴细胞相比,对照的转录组谱分析在神经嵴分层和早期迁移期间鉴定了新的BMP靶标,包括在BMP抑制后上调的Notch途径的靶标。这些结果表明,在早期迁移颅神经嵴的BMP和Notch通路之间的潜在串扰,并提供了新的见解BMP信号调节机制在颅面发育早期。
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.
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