β-Catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse
β-Catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse
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DOI：
10.1083/jcb.200403050
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发表时间：
2004-08-02
影响因子：
7.8
通讯作者：
Dejana, E
中科院分区：
文献类型：
--
作者：
Liebner, S;Cattelino, A;Dejana, E
在心脏发育过程中，房室（AV）区域的心内膜细胞经历tgfp依赖性上皮-间质转化（EMT）并侵袭下层的心脏果冻。这一过程产生心内膜垫，房室瓣膜和部分隔膜起源于心内膜垫。在本文中，我们发现在小鼠胚胎和AV外植体中，缺乏内皮β -连环蛋白的小鼠，TGFP对心内膜EMT的诱导受到强烈抑制，导致心脏垫形成不足。使用wnt信号报告小鼠品系，我们在体内和体外证明了心脏垫中的EMT伴随着β -catenin/TCF/ left转录活性的激活。在培养的内皮细胞中，TGFbeta2诱导α -平滑肌肌动蛋白（alphaSMA）表达。这一过程在p-catenin缺失的细胞中被强烈地减弱，尽管TGFbeta2诱导的smad磷酸化没有改变。这些数据表明β -catenin/TCF/ left转录活性参与心脏缓冲的形成，并提示tgf - β和wnt信号通路在诱导内皮-间质转化中的相互作用。
During heart development endocardial cells within the atrio-ventricular (AV) region undergo TGFP-dependent epithelial-mesenchymal transformation (EMT) and invade the underlying cardiac jelly. This process gives rise to the endocardial cushions from which AV valves and part of the septum originate. In this paper we show that in mouse embryos and in AV explants TGFP induction of endocardial EMT is strongly inhibited in mice deficient for endothelial beta-catenin, leading to a lack of heart cushion formation. Using a Wnt-signaling reporter mouse strain, we demonstrated in vivo and ex vivo that EMT in heart cushion is accompanied by activation of beta-catenin/TCF/Lef transcriptional activity. In cultured endothelial cells, TGFbeta2 induces alpha-smooth muscle actin (alphaSMA) expression. This process was strongly reduced in p-catenin null cells, although TGFbeta2 induced smad phosphorylation was unchanged. These data demonstrate an involvement of beta-catenin/TCF/Lef transcriptional activity in heart cushion formation, and suggest an interaction between TGFbeta and Wnt-signaling pathways in the induction of endothelial-mesenchymal transformation.