Parisot Pauline, Mesbah Karim, Théveniau-Ruissy Magali, Kelly Robert G
Developmental Biology Institute of Marseilles-Luminy, UMR 6216/CNRS, Université de la Méditerranée, Marseilles, France.
Birth Defects Res A Clin Mol Teratol. 2011 Jun;91(6):477-84. doi: 10.1002/bdra.20803. Epub 2011 May 17.
Conotruncal congenital heart defects, including defects in septation and alignment of the ventricular outlets, account for approximately a third of all congenital heart defects. Failure of the left ventricle to obtain an independent outlet results in incomplete separation of systemic and pulmonary circulation at birth. The embryonic outflow tract, a transient cylinder of myocardium connecting the embryonic ventricles to the aortic sac, plays a critical role in this process during normal development. The outflow tract (OFT) is derived from a population of cardiac progenitor cells called the second heart field that contributes to the arterial pole of the heart tube during cardiac looping. During septation, the OFT is remodeled to form the base of the ascending aorta and pulmonary trunk. Tbx1, the major candidate gene for DiGeorge syndrome, is a critical transcriptional regulator of second heart field development. DiGeorge syndrome patients are haploinsufficient for Tbx1 and present a spectrum of conotruncal anomalies including tetralogy of Fallot, pulmonary atresia, and common arterial trunk. In this review, we focus on the role of Tbx1 in the regulation of second heart field deployment and, in particular, in the development of a specific population of myocardial cells at the base of the pulmonary trunk. Recent data characterizing additional properties and regulators of development of this region of the heart, including the retinoic acid, hedgehog, and semaphorin signaling pathways, are discussed. These findings identify future subpulmonary myocardium as the clinically relevant component of the second heart field and provide new mechanistic insight into a spectrum of common conotruncal congenital heart defects.
圆锥干先天性心脏缺陷，包括心室流出道的分隔和排列缺陷，约占所有先天性心脏缺陷的三分之一。左心室未能获得独立的流出道会导致出生时体循环和肺循环不完全分离。胚胎流出道是连接胚胎心室与主动脉囊的一段短暂的心肌圆柱体，在正常发育过程中，该结构在此过程中起着关键作用。流出道（OFT）起源于一群称为第二心脏场的心脏祖细胞，在心脏成环过程中，这群细胞对心管的动脉极有贡献。在分隔过程中，流出道会重塑形成升主动脉和肺动脉干的基部。Tbx1是DiGeorge综合征的主要候选基因，是第二心脏场发育的关键转录调节因子。DiGeorge综合征患者的Tbx1基因剂量不足，会出现一系列圆锥干异常，包括法洛四联症、肺动脉闭锁和共同动脉干。在这篇综述中，我们重点关注Tbx1在调节第二心脏场部署中的作用，特别是在肺动脉干基部特定心肌细胞群的发育中的作用。本文还讨论了最近关于心脏该区域发育的其他特性和调节因子的数据，包括视黄酸、刺猬和信号素信号通路。这些发现确定了未来肺动脉下心肌是第二心脏场的临床相关组成部分，并为一系列常见的圆锥干先天性心脏缺陷提供了新的机制性见解。
