Cdc42 activation by endothelin regulates neural crest cell migration in the cardiac outflow tract.
Cdc42 activation by endothelin regulates neural crest cell migration in the cardiac outflow tract.
复制标题
内皮素激活 Cdc42 调节心脏流出道中的神经嵴细胞迁移。
DOI：
10.1002/dvdy.75
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Ruest,LBruno
中科院分区：
文献类型：
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作者：
Fritz,KatrinaR;Zhang,Yanping;Ruest,LBruno
背景先天性心血管畸形是影响儿童最常见的出生缺陷。这些缺陷中的一些发生在从神经嵴细胞发育的结构中。调节心脏神经嵴细胞（CNCC）发育的关键信号通路之一涉及内皮素A受体（Ednra）。然而，CNCC.ResultsThe命运映射CNCC在Ednra胚胎的确切功能Ednra信号表示，这些细胞的迁移是异常的心脏流出道（OFT），但不是在咽弓。CNCC迁移的过早停滞独立于CNCC增殖和凋亡变化以及主要基因表达变化而发生。在突变胚胎中的小GTP酶的Rho家族的分析表明，Cdc42未能正常定位在CNCC迁移的OFT。在培养的胚胎中Cdc42活性的抑制再现了在Ednra小鼠中观察到的迁移表型。进一步的分析表明，Cdc42是由内皮素激活的信号通路的一部分，特别是在OFT CNCC，以控制其migration.ConclusionsThese结果表明，激活Cdc42内皮素信号是重要的CNCC迁移在OFT，但这一途径不参与下颌或咽弓动脉图案。
BackgroundCongenital cardiovascular malformations are the most common birth defects affecting children. Several of these defects occur in structures developing from neural crest cells. One of the key signaling pathways regulating cardiac neural crest cell (CNCC) development involves the endothelin‐A receptor (Ednra). However, the exact function of Ednra signaling in CNCC is unknown.ResultsThe fate mapping of CNCC inEdnraembryos indicated that the migration of these cells is aberrant in the cardiac outflow tract (OFT), but not in the pharyngeal arches. This premature arrest of CNCC migration occurs independently of CNCC proliferation and apoptosis changes and major gene expression changes. Analysis of the Rho family of small GTPases in the mutant embryos revealed that Cdc42 failed to localize normally in the CNCC migrating in the OFT. The inhibition of Cdc42 activity in cultured embryos recapitulated the migratory phenotype observed inEdnramice. Further analyses revealed that Cdc42 is part of the signaling pathway activated by endothelin specifically in OFT CNCC to control their migration.ConclusionsThese results indicated that the activation of Cdc42 by endothelin signaling is important for CNCC migration in the OFT but this pathway is not involved in mandibular or pharyngeal arch artery patterning.