Zaffran Stéphane, Kelly Robert G, Meilhac Sigolène M, Buckingham Margaret E, Brown Nigel A
Department of Developmental Biology, CNRS URA 2578, Pasteur Institute, 25 rue du Dr Roux, Paris, 75015, France.
Circ Res. 2004 Aug 6;95(3):261-8. doi: 10.1161/01.RES.0000136815.73623.BE. Epub 2004 Jun 24.
The mammalian heart develops from a primary heart tube, which is formed by fusion of bilateral cardiac territories in which myocardial and endothelial cells have already begun to differentiate from splanchnic mesoderm. A population of myocardial precursors has been identified in pharyngeal mesoderm, anterior to the early heart tube. Cell labeling studies have indicated that this novel territory, called the anterior heart field (AHF), gives rise to the myocardial wall of the outflow tract. We now report that not only the myocardium of the outflow tract but also myocardial cells of the embryonic right ventricle are derived from this source. Explants of pharyngeal mesoderm or of the early heart tube were cultured from transgenic mice in which transgene expression marks different regions of the heart. Pharyngeal mesoderm from 5 to 7 somite embryos gives rise to cardiomyocytes with right ventricular and outflow tract identities, whereas the heart tube as this stage has an essentially left ventricular identity. DiI labeling confirms that the early heart tube is destined to contribute to the embryonic left ventricle and indicates that right ventricular myocardium is added from extracardiac mesoderm. Retrospective clonal analysis of the heart at embryonic day (E) 10.5 reveals the existence of a clonal boundary in the interventricular region, which appears during ventricular septation, underlining different origins of the two ventricular compartments. This study demonstrates the differences in the embryological origin of right and left ventricular myocardium, which has important implications for congenital heart disease.
哺乳动物的心脏由一个原始心管发育而来,原始心管是由双侧心脏区域融合形成的,在这些区域中,心肌细胞和内皮细胞已开始从脏壁中胚层分化出来。在早期心管前方的咽中胚层中已鉴定出一群心肌前体细胞。细胞标记研究表明,这个新区域,即前心场(AHF),产生了流出道的心肌壁。我们现在报告,不仅流出道的心肌,而且胚胎右心室的心肌细胞也来源于此。从转基因小鼠中培养咽中胚层或早期心管的外植体,其中转基因表达标记心脏的不同区域。来自5至7体节胚胎的咽中胚层产生具有右心室和流出道特征的心肌细胞,而此阶段的心管基本上具有左心室特征。DiI标记证实早期心管注定会对胚胎左心室有贡献,并表明右心室心肌是从心外中胚层添加的。对胚胎第10.5天(E10.5)心脏的回顾性克隆分析揭示了室间隔形成期间在室间区域存在克隆边界,突显了两个心室腔室的不同起源。这项研究证明了右心室和左心室心肌胚胎起源的差异,这对先天性心脏病具有重要意义。