Tgfβ signaling is required for atrioventricular cushion mesenchyme remodeling during in vivo cardiac development
Tgfβ signaling is required for atrioventricular cushion mesenchyme remodeling during in vivo cardiac development
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DOI：
10.1242/dev.02597
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发表时间：
2006-11-15
期刊：
影响因子：
4.6
通讯作者：
Baldwin, H. Scott
中科院分区：
文献类型：
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作者：
Jiao, Kai;Langworthy, Melissa;Baldwin, H. Scott
转化生长因子β（TGF β）信号通路在许多生物学过程中起着至关重要的作用。为了了解Tgf β信号在体内心脏发生过程中的作用并克服Tgfbr 2（-/-）胚胎的早期致死性，我们应用Cre/loxp系统特异性地在小鼠胚胎的心肌或内皮中抑制Tgfbr 2。我们的研究结果表明，心肌中的Tgfbr 2是在大多数胚胎的心脏发生。相反的预测，从以前的体外胶原凝胶检测的结果，Tgfbr 2的失活的endoepithelium不阻止房室垫间充质的形成，反对其在上皮间充质转化在体内的重要作用。我们进一步证明，Tgf β信号传导是必要的房室管和心脏循环的正确重塑，并在Tgf β信号的扰动导致双入口左心室（DILV）的缺陷。因此，我们的研究为DILV提供了一种独特的小鼠遗传模型，其进一步表征表明了该缺陷的潜在细胞机制。
The transforming growth factor beta (Tgf beta) signaling pathway plays crucial roles in many biological processes. To understand the role(s) of Tgf beta signaling during cardiogenesis in vivo and to overcome the early lethality of Tgfbr2(-/-) embryos, we applied a Cre/loxp system to specifically inactivate Tgfbr2 in either the myocardium or the endothelium of mouse embryos. Our results show that Tgfbr2 in the myocardium is dispensable for cardiogenesis in most embryos. Contrary to the prediction from results of previous in vitro collagen gel assays, inactivation of Tgfbr2 in the endocardium does not prevent atrioventricular cushion mesenchyme formation, arguing against its essential role in epithelium-mesenchyme transformation in vivo. We further demonstrate that Tgf beta signaling is required for the proper remodeling of the atrioventricular canal and for cardiac looping, and that perturbation in Tgf beta signaling causes the double-inlet left ventricle (DILV) defect. Thus, our study provides a unique mouse genetic model for DILV, further characterization of which suggests a potential cellular mechanism for the defect.