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首页> 外文期刊>Development >Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation.
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Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation.

机译:Foxp1调节心脏流出道,心内膜垫形态发生以及心肌细胞增殖和成熟。

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We have recently described a new subfamily of Fox genes, Foxp1/2/4, which are transcriptional repressors and are thought to regulate important aspects of development in several tissues, including the lung, brain, thymus and heart. Here, we show that Foxp1 is expressed in the myocardium as well as the endocardium of the developing heart. To further explore the role of Foxp1 in cardiac development, we inactivated Foxp1 through gene targeting in embryonic stem cells. Foxp1 mutant embryos have severe defects in cardiac morphogenesis, including outflow tract septation and cushion defects, a thin ventricular myocardial compact zone caused by defects in myocyte maturation and proliferation, and lack of proper ventricular septation. These defects lead to embryonic death at E14.5 and are similar to those observed in other mouse models of congenital heart disease, including Sox4 and Nfatc1 null embryos. Interestingly, expression of Sox4 in the outflow tract and cushions of Foxp1 null embryos is significantly reduced, while remodeling of the cushions is disrupted, as demonstrated by reduced apoptosis and persistent Nfatc1 expression in the cushion mesenchyme. Our results reveal a crucial role for Foxp1 in three aspects of cardiac development: (1) outflow tract development and septation, (2) tissue remodeling events required for cardiac cushion development, and (3) myocardial maturation and proliferation.
机译:我们最近描述了Fox基因的一个新亚家族Foxp1 / 2/4,它是转录阻遏物,被认为可以调节包括肺,脑,胸腺和心脏在内的多个组织中重要的发育方面。在这里,我们显示Foxp1在心脏以及正在发育的心脏的心内膜中表达。为了进一步探索Foxp1在心脏发育中的作用,我们通过靶向胚胎干细胞中的基因来灭活Foxp1。 Foxp1突变体胚胎在心脏形态发生方面有严重缺陷,包括流出道分隔和垫层缺陷,由心肌细胞成熟和增​​殖缺陷引起的薄型心室心肌致密区,以及缺乏适当的心室分隔。这些缺陷导致胚胎在E14.5处死亡,并且与其他先天性心脏病小鼠模型(包括Sox4和Nfatc1空胚)中观察到的相似。有趣的是,Sox4在Foxp1无效胚的流出道和垫子中的表达显着降低,而垫子的重塑被破坏,这由垫子间充质细胞凋亡减少和Nfatc1持续表达所证实。我们的结果揭示了Foxp1在心脏发育的三个方面的关键作用:(1)流出道发育和分隔,(2)心脏垫层发育所需的组织重塑事件,以及(3)心肌成熟和增殖。

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