Heart Failure Research Center, Department of Anatomy, Embryology & Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Acta Physiol (Oxf). 2013 Apr;207(4):588-615. doi: 10.1111/apha.12061. Epub 2013 Feb 1.
Perturbations in cardiac development result in congenital heart disease, the leading cause of birth defect-related infant morbidity and mortality. Advances in cardiac developmental biology have significantly augmented our understanding of signalling pathways and transcriptional networks underlying heart formation. Cardiogenesis is initiated with the formation of mesodermal multipotent cardiac progenitor cells and is governed by cross-talk between developmental cues emanating from endodermal, mesodermal and ectodermal cells. The molecular and transcriptional machineries that direct the specification and differentiation of these cardiac precursors are part of an evolutionarily conserved programme that includes the Nkx-, Gata-, Hand-, T-box- and Mef2 family of transcription factors. Unravelling the hierarchical networks governing the fate and differentiation of cardiac precursors is crucial for our understanding of congenital heart disease and future stem cell-based and gene therapies. Recent molecular and genetic lineage analyses have revealed that subpopulations of cardiac progenitor cells follow distinctive specification and differentiation paths, which determine their final contribution to the heart. In the last decade, progenitor cells that contribute to the arterial pole and right ventricle have received much attention, as abnormal development of these cells frequently results in congenital defects of the aortic and pulmonary outlets, representing the most commonly occurring congenital cardiac defects. In this review, we provide an overview of the building plan of the vertebrate four-chambered heart, with a special focus on cardiac progenitor cell specification, differentiation and deployment during arterial pole development.
心脏发育异常会导致先天性心脏病，这是导致婴儿发病率和死亡率与出生缺陷相关的主要原因。心脏发育生物学的进步极大地增进了我们对心脏形成所涉及的信号通路和转录网络的理解。心肌发生始于中胚层多能性心肌祖细胞的形成，并受来自内胚层、中胚层和外胚层细胞的发育线索之间的相互作用调控。指导这些心肌前体细胞的特化和分化的分子和转录机制是一个进化上保守的程序的一部分，其中包括 Nkx、Gata、Hand、T-box 和 Mef2 转录因子家族。揭示控制心肌前体细胞命运和分化的层次网络对于我们理解先天性心脏病以及未来基于干细胞和基因治疗的方法至关重要。最近的分子和遗传谱系分析表明，心肌祖细胞的亚群遵循独特的特化和分化途径，这些途径决定了它们对心脏的最终贡献。在过去的十年中，对有助于动脉干和右心室的祖细胞进行了大量研究，因为这些细胞的异常发育经常导致主动脉和肺动脉出口的先天性缺陷，这是最常见的先天性心脏缺陷。在这篇综述中，我们概述了脊椎动物四腔心脏的构建计划，特别关注动脉干发育过程中心肌祖细胞的特化、分化和部署。
