BMP type II receptor regulates positioning of outflow tract and remodeling of atrioventricular cushion during cardiogenesis.
BMP type II receptor regulates positioning of outflow tract and remodeling of atrioventricular cushion during cardiogenesis.
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DOI：
10.1016/j.ydbio.2009.04.032
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发表时间：
2009-07-15
影响因子：
2.7
通讯作者：
Bloch, Kenneth D.
中科院分区：
文献类型：
--
作者：
Beppu, Hideyuki;Malhotra, Rajeev;Beppu, Yuko;Lepore, John J.;Parmacek, Michael S.;Bloch, Kenneth D.
关键词：
骨形态发生蛋白（BMP）信号通过I型和II型受体参与心脏发生的多个过程。为了研究BMP II型受体（BMPRII）在心脏发育中的作用，在原肠胚形成过程中，使用Mox2-Cre转基因在整个胚胎中删除BMPRII基因。BMPRIIflox /−;Mox2-Cre小鼠出现双出口右心室、室间隔缺损（VSD）、房室（AV）垫缺损、瓣叶增厚等心脏缺陷。为了表征BMPRII在心脏发生中的组织特异性功能，采用了一系列Cre转基因（αMHC-, Tie2-， Wnt1-和SM22α-Cre）。有趣的是，当使用Mox2-Cre、αMHC-Cre或SM22α-Cre转基因去除心肌细胞中的BMPRII基因时，心肌发育正常，这表明其他BMP II型受体的信号传导可能弥补了心肌细胞中BMPRII的缺失。在BMPRIIflox/−中发现房间隔缺损、膜性室间隔缺损和瓣叶增厚等房室缓冲缺损；Tie2-Cre老鼠。BMPRIIflox/−观察到主动脉定位异常；Wnt1-Cre和BMPRIIflox/−；SM22αcre老鼠。综上所述，这些结果表明心内膜BMPRII的表达是室间隔形成和瓣膜形成所必需的。此外，流出道缓冲层中BMPRII的间质表达对于主动脉的正确定位是必需的。
Signaling of bone morphogenetic protein (BMP) via type I and type II receptors is involved in multiple processes contributing to cardiogenesis. To investigate the role of the BMP type II receptor (BMPRII) in heart development, the BMPRII gene was deleted throughout the embryo during gastrulation using a Mox2-Cre transgene. BMPRIIflox/−;Mox2-Cre mice exhibited cardiac defects including double-outlet right ventricle, ventricular septal defect (VSD), atrioventricular (AV) cushion defects, and thickened valve leaflets. To characterize the tissue-specific functions of BMPRII in cardiogenesis, a series of Cre transgenes (αMHC-, Tie2-, Wnt1-, and SM22α-Cre) was employed. Interestingly, myocardial development was normal when the BMPRII gene was deleted in myocardial cells using Mox2-Cre, αMHC-Cre, or SM22α-Cre transgenes, suggesting that signaling by other BMP type II receptors may compensate for the absence of BMPRII in the myocardial cells. AV cushion defects including atrial septal defect, membranous VSD, and thickened valve leaflets were found in BMPRIIflox/−;Tie2-Cre mice. Abnormal positioning of the aorta was observed in BMPRIIflox/−;Wnt1-Cre and BMPRIIflox/−;SM22α-Cre mice. Taken together, these results demonstrate that endocardial BMPRII expression is required for septal formation and valvulogenesis. Moreover, mesenchymal BMPRII expression in the outflow tract cushion is required for proper positioning of the aorta.
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影响因子：
4.6
作者：
Délot, EC;Bahamonde, ME;Lyons, KM
通讯作者：
Lyons, KM
影响因子：
2.7
作者：
Beppu, H;Kawabata, M;Miyazono, K
通讯作者：
Miyazono, K
影响因子：
20.1
作者：
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通讯作者：
Christoffels, VM
DOI：
10.1073/pnas.042390499
发表时间：
2002-03-05
影响因子：
11.1
作者：
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通讯作者：
Schneider, MD
影响因子：
5.3
作者：
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通讯作者：
Hata, Akiko