Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3
Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3
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DOI：
10.1073/pnas.042390499
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发表时间：
2002-03-05
影响因子：
11.1
通讯作者：
Schneider, MD
中科院分区：
文献类型：
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作者：
Gaussin, V;Van de Putte, T;Schneider, MD
骨形态发生蛋白受体(BMPs)是转化生长因子-β(TGFbeta)超家族的成员，在心脏发育过程中持续表达，但缺乏11型或IA型BMP受体的小鼠在原肠形成时死亡，不能用于评估未来在心脏形成中的潜在作用。在这里，我们使用CRE/LOX系统对心肌细胞特异性的IA型BMP受体ALK3进行删除。ALK3在妊娠中期是小梁、致密心肌、室间隔和心内膜垫正常发育所必需的。缺乏ALK3的心肌特别缺乏TGFbeta2的表达，TGFbeta2是一种已建立的缓冲形态发生的旁分泌介质，因此，ALK3在心脏器官发生中对心肌细胞依赖的功能和信号是必不可少的，而不仅仅是卵筒阶段。
Receptors for bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGFbeta) superfamily, are persistently expressed during cardiac development, yet mice lacking type 11 or type IA BMP receptors die at gastrulation and cannot be used to assess potential later roles in creation of the heart. Here, we used a Cre/lox system for cardiac myocyte-specific deletion of the type IA BMP receptor, ALK3. ALK3 was specifically required at mid-gestation for normal development of the trabeculae, compact myocardium, interventricular septum, and endocardial cushion. Cardiac muscle lacking ALK3 was specifically deficient in expressing TGFbeta2, an established paracrine mediator of cushion morphogenesis, Hence, ALK3 is essential, beyond just the egg cylinder stage, for myocyte-dependent functions and signals in cardiac organogenesis.