Department of Anatomy, Embryology & Physiology, Academic Medical Center, Amsterdam, the Netherlands.
J Anat. 2012 Apr;220(4):336-49. doi: 10.1111/j.1469-7580.2012.01474.x. Epub 2012 Feb 1.
Labeling experiments in chicken and mouse embryos have revealed important roles for different cell lineages in the development of the cardiac arterial pole. These data can only fully be exploited when integrated into the continuously changing morphological context and compared with the patterns of gene expression. As yet, studies on the formation of separate ventricular outlets and arterial trunks in the human heart are exclusively based on histologically stained sections. So as to expand these studies, we performed immunohistochemical analyses of serially sectioned human embryos, along with three-dimensional reconstructions. The development of the cardiac arterial pole involves several parallel and independent processes of formation and fusion of outflow tract cushions, remodeling of the aortic sac and closure of an initial aortopulmonary foramen through formation of a transient aortopulmonary septum. Expression patterns of the transcription factors ISL1, SOX9 and AP2α show that, in addition to fusion of the SOX9-positive endocardial cushions, intrapericardial protrusion of pharyngeal mesenchyme derived from the neural crest contributes to the separation of the developing ascending aorta from the pulmonary trunk. The non-adjacent walls of the intrapericardial arterial trunks are formed through addition of ISL1-positive cells to the distal outflow tract, while the facing parts of the walls form from the protruding mesenchyme. The morphogenetic steps, along with the gene expression patterns reported in this study, are comparable to those observed in the mouse. They confirm the involvement of mesenchymal tissues derived from endocardium, mesoderm and migrating neural crest cells in the process of initial septation of the distal part of the outflow tract, and its subsequent separation into discrete intrapericardial arterial trunks.
鸡和鼠胚胎的标记实验揭示了不同细胞谱系在心脏动脉干发育中的重要作用。这些数据只有在整合到不断变化的形态背景中，并与基因表达模式进行比较时，才能得到充分利用。迄今为止，关于人心脏中单独的心室出口和动脉干形成的研究仅基于组织学染色切片。为了扩展这些研究，我们对连续切片的人类胚胎进行了免疫组织化学分析，并进行了三维重建。心脏动脉干的发育涉及几个平行和独立的流出道垫形成和融合、主动脉囊重塑以及通过形成短暂的主动脉肺动脉隔来闭合初始的主动脉肺动脉孔的过程。转录因子 ISL1、SOX9 和 AP2α 的表达模式表明，除了 SOX9 阳性心内膜垫的融合之外，来自神经嵴的咽中胚层的心包内突起有助于将正在发育的升主动脉与肺动脉分离。心包内动脉干的非相邻壁是通过将 ISL1 阳性细胞添加到远端流出道来形成的，而壁的突出部分则来自突起的间质。这些形态发生步骤以及本研究中报告的基因表达模式与在小鼠中观察到的相似。它们证实了来源于心内膜、中胚层和迁移的神经嵴细胞的间充质组织在流出道远端初始分隔过程中的参与，以及随后将其分离为离散的心包内动脉干。
