Id4 functions downstream of Bmp signaling to restrict TCF function in endocardial cells during atrioventricular valve development
Id4 functions downstream of Bmp signaling to restrict TCF function in endocardial cells during atrioventricular valve development
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DOI：
10.1016/j.ydbio.2016.02.003
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发表时间：
2016-04-01
影响因子：
2.7
通讯作者：
Reischauer, Sven
中科院分区：
文献类型：
--
作者：
Ahuja, Suchit;Dogra, Deepika;Reischauer, Sven
房室管（AVC）连接心脏的心房和心室，其形成对于心脏瓣膜的发育、心室分隔和心脏传导系统的形成至关重要。因此，AVC 形成的问题可能导致先天性缺陷，包括心律失常和不完全心脏间隔。虽然我们对早期心管形成的了解相对全面，但关于调节 AVC 形成的基因仍有许多待研究。在这里，我们确定了基本螺旋-环-螺旋因子 Id4 在斑马鱼 AVC 瓣膜发育和功能中的新作用。 id4首先在AVC心内膜中表达，随后在心房中表达得更高。 TALEN 诱导的 id4 失活导致热应激条件下 AV 管的血流逆流，表明 AV 瓣膜功能缺陷。在分子水平上，我们发现 id4 失活会导致对 AVC 和 AV 瓣膜形成重要的几个基因的错误表达，包括 bmp4 和 sppl。我们进一步表明，id4 似乎通过调节发育中的 AVC 心内膜中的 Wnt 信号来控制对 AV 瓣膜做出贡献的心内膜细胞的数量。 (C) 2016 Elsevier Inc. 保留所有权利。
The atrioventricular canal (AVC) connects the atrial and ventricular chambers of the heart and its formation is critical for the development of the cardiac valves, chamber septation and formation of the cardiac conduction system. Consequently, problems in AVC formation can lead to congenital defects ranging from cardiac arrhythmia to incomplete cardiac septation. While our knowledge about early heart tube formation is relatively comprehensive, much remains to be investigated about the genes that regulate AVC formation. Here we identify a new role for the basic helix-loop-helix factor Id4 in zebrafish AVC valve development and function. id4 is first expressed in the AVC endocardium and later becomes more highly expressed in the atrial chamber. TALEN induced inactivation of id4 causes retrograde blood flow at the AV canal under heat induced stress conditions, indicating defects in AV valve function. At the molecular level, we found that id4 inactivation causes misexpression of several genes important for AVC and AV valve formation including bmp4 and sppl. We further show that id4 appears to control the number of endocardial cells that contribute to the AV valves by regulating Wnt signaling in the developing AVC endocardium. (C) 2016 Elsevier Inc. All rights reserved.