Notch2 is required for the proliferation of cardiac neural crest-derived smooth muscle cells
Notch2 is required for the proliferation of cardiac neural crest-derived smooth muscle cells
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DOI：
10.1002/dvdy.21502
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发表时间：
2008-04-01
影响因子：
2.5
通讯作者：
McCright, Brent
中科院分区：
文献类型：
--
作者：
Varadkar, Prajakta;Kraman, Matthew;McCright, Brent
Notch受体及其配体的突变已被确定为人类先天性心脏病的原因，表明Notch信号通路在心脏发育过程中的重要性。在我们的研究中，我们使用Cre-Lox技术使几种心肌细胞系中的Notch2失活，以确定哺乳动物心脏发育过程中对Notch2的功能需求。心脏神经脊细胞中Notch2的失活导致动脉和肺动脉异常狭窄，这是由于平滑肌组织减少所致。平滑肌组织的减少不是由于细胞迁移缺陷，而是由于妊娠中后期平滑肌细胞增殖减少所致。我们的发现表明，Notch2是心脏流出道正常形成所需的自主细胞，并为深入了解Notch2在血管平滑肌发育和与Alagille综合征相关的心血管缺陷中的作用提供了线索。
Mutations in Notch receptors and their ligands have been identified as the cause of human congenital heart diseases, indicating the importance of the Notch signaling pathway during heart development. In our study, we use Cre-Lox technology to inactivate Notch2 in several cardiac cell lineages to determine the functional requirements for Notch2 during mammalian heart development. Inactivation of Notch2 in cardiac neural crest cells resulted in abnormally narrow aortas and pulmonary arteries due to a decrease in smooth muscle tissue. The reduction in smooth muscle tissue was not due to cell migration defects but instead was found to be caused by less proliferation in smooth muscle cells during mid to late gestation. Our findings demonstrate that Notch2 is required cell autonomously for proper formation of the heart outflow tract and provides insights into the role of Notch2 in vascular smooth muscle development and the cardiovascular defects associated with Alagille syndrome.