Fig. 2.

Early cardiac development. a Cardiac cell lineage and specification during development demonstrating the commitment of pluripotent cells toward mature cardiac cell types within the heart development. b Schematic of cardiac morphogenesis in humans. At the second week of gestation, the cardiogenic mesodermal cells migrate toward the anterior side of the embryo to form the FHF or cardiac crescent and SHF that are specified to form specific segments of the PHT, which is patterned along the anteroposterior axis to form the various regions and chambers of the looped and mature heart during weeks 3 and 4. The FHF gives rise to the beating PHT and will eventually give rise to the LV and parts of the right and left atria (RA and LA, respectively). The SHF, located behind the PHT and within the pharyngeal mesoderm by gestational week 3, will contribute to the formation of the RV, parts of the atria and outflow tract, and later to the base of the aorta and pulmonary artery. At gestational week 3, the cells at the venous pole contribute to the formation of the superior and inferior vena cavas (IVC, respectively). By gestational week 4, the cardiac neural crest cells migrate in from the dorsal neural tube, forming smooth muscle cells within the aortic and pulmonary arteries. In addition, the proepicardial organ formed by the proepicardial progenitor cell clusters later contributes to the formation of the epicardium. The 4 chambers form by the end of week 7. Wnt, Wingles integrated; FGF, fibroblast growth factor; BMP, bone morphogenetic proteins; FHF, first heart field; SHF, second heart field; OFT, outflow tract; PHT, primary heart tube; PM, pharyngeal mesoderm; VP, venous pole; CNCCs, cardiac neural crest cells; LV, left ventricle; RV, right ventricle; PEO, proepicardial organ; SVC, superior vena cavas; IVC, inferior vena cavas; EPC, epicardium; and PA, pulmonary artery.