Consequently, cardiac mesoderm progenitors are among the first cells to ingress through the PS during gastrulation. 1D section detail in box) determines the fate of gastrulating cells. Fate mapping studies in mouse and chicken embryos have shown that time and location of cell ingression through the primitive streak (PS) ( Fig. The embryonic heart is the first organ to function during development. Here we will describe “the lives” of these different cardiac progenitors, from their embryonic specification to their differentiation into mature cells of the heart, and we will discuss how this knowledge could inform the future development of novel therapies for cardiovascular heart disease.Ĭardiogenic Mesoderm Progenitors in Early Vertebrate Cardiogenesis Cardiac valve development and septation of the heart is also critically dependent on proper CNC development ( Fig. 1B).įinally, the CNC progenitors give rise to the distal smooth muscle cells of the OFT and the aorticopulmonary ridge as well as to the autonomous nervous system of the heart. Additionally, interaction of the epicardium with the underlying myocardium is crucial for chamber maturation and ventricular muscle growth ( Fig. Progenitors originating from the PE comprise the epicardium and differentiate into interstitial fibroblasts embedded in the myocardium, vascular smooth muscle cells and endothelial cells of the coronary vessels, and some myocytes, mainly in the atrioventricular septum. Additionally, these progenitors contribute cells to the endocardium, the conduction system, and the aortic and pulmonary cushions ( Fig. The cardiogenic mesoderm, which harbors the so-called first and second heart fields (FHF and SHF), forms the major proportion of the ventricular, atrial, and outflow tract (OFT) myocardium. AA, Aortic arch ant, anterior AO, dorsal aorta CNCC, cardiac neural crest cells do, dorsal EPI, epicardium FHF, first heart field HF, headfolds IVS, interventricular septum L, left LA, left atrium LV, left ventricle OFT, outflow tract PE, proepicardium PhA, pharyngeal arch PLA, primitive left atrium post, posterior PRA, primitive right atrium PS, primitive streak PT, pulmonary trunk R, right RA, right atrium RV, right ventricle SHF, second heart field SMCs, smooth muscle cells ven, ventral. ( H) At E14.5, the heart shows four fully septated chambers and a septated outflow tract connected to the pulmonary trunk and the dorsal aorta. ( G) At E10.5, cardiac neural crest and proepicardial cells contribute to the heart, which already shows a defined four-chamber morphology. ( F) At E8.5, the linear heart tube undergoes rightward looping. SHF progenitors will gradually migrate into the linear heart tube and differentiate then. At E8.0, the cardiac crescent forms the beating, linear heart tube. FHF progenitor cells start to differentiate. The first heart fields fuse at the midline thereby forming the cardiac crescent caudal to the headfolds. ( E) At E7.5, the first and second heart fields (FHF and SHF) are discernible. ( D) At E6.5, mesodermal progenitors ingress through the primitive streak (PS) and migrate away from the PS (illustrated in the box showing a transverse section) to form the heart fields located in the splanchnic mesoderm. ( A) Cardiogenic mesoderm, ( B) proepicardium/epicardium, and ( C) cardiac neural crest cell lineage diversification. Embryonic heart progenitor contributions to different cardiac compartments and cell types during heart morphogenesis in mouse development.
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