Cell autonomous requirement of endocardial Smad4 during atrioventricular cushion development in mouse embryos.
Cell autonomous requirement of endocardial Smad4 during atrioventricular cushion development in mouse embryos.
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DOI：
10.1002/dvdy.22493
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发表时间：
2011-01
影响因子：
2.5
通讯作者：
Jiao, Kai
中科院分区：
文献类型：
--
作者：
Song, Langying;Zhao, Mei;Wu, Bingruo;Zhou, Bin;Wang, Qin;Jiao, Kai
房室垫是房室间隔和瓣膜的前体。在这项研究中，我们研究了Smad4在AV垫发展过程中的作用，使用条件基因失活的方法。我们发现Smad4的内皮/内皮细胞失活导致细胞减少的AV垫缺陷，并且细胞增殖减少和细胞凋亡增加都有助于缺陷。在突变胚中，多个对垫状体发育至关重要的基因表达下调。在胶原凝胶试验中，与对照外植体相比，突变体AV外植体中形成的间充质细胞数量显著减少，表明突变体中缓冲间充质形成的减少不太可能继发于其总体血管系统异常。使用先前开发的永生内皮细胞系，我们表明Smad4是BMP信号刺激的Tbx20和Gata4上调所需的。因此，我们的数据共同支持心内膜Smad 4调节AV垫发育的细胞自主需求。
Atrioventricular (AV) cushions are the precursors of AV septum and valves. In this study, we examined roles of Smad4 during AV cushion development using a conditional gene inactivation approach. We found that endothelial/endocardial inactivation of Smad4 led to the hypocellular AV cushion defect and that both reduced cell proliferation and increased apoptosis contributed to the defect. Expression of multiple genes critical for cushion development was down-regulated in mutant embryos. In collagen gel assays, the number of mesenchymal cells formed is significantly reduced in mutant AV explants compared to that in control explants, suggesting that the reduction of cushion mesenchyme formation in mutants is unlikely secondary to their gross vasculature abnormalities. Using a previously developed immortal endocardial cell line, we showed that Smad4 is required for BMP signaling- stimulated upregulation of Tbx20 and Gata4. Therefore, our data collectively support the cell-autonomous requirement of endocardial Smad4 in regulating AV cushion development.
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影响因子：
2.7
作者：
BERNANKE, DH;MARKWALD, RR
通讯作者：
MARKWALD, RR
影响因子：
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作者：
Hussein, SM;Duff, EK;Sirard, C
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影响因子：
11.2
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DOI：
10.1073/pnas.042390499
发表时间：
2002-03-05
影响因子：
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作者：
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通讯作者：
Schneider, MD
影响因子：
2.7
作者：
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通讯作者：
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