Fig. 1. Origin and lineage relationship of cardiac cell types. (A) Contribution of the three populations of embryonic heart progenitors, cardiogenic mesoderm (red), cardiac neural crest (purple) and proepicardial organ (yellow) to different heart compartments during cardiac morphogenesis in the mouse. Progenitors of the cardiogenic mesoderm are first recognizable under the head folds (HFs) of the embryo at E7.5, then move ventrally to the midline (ML) and form initially the linear heart tube and ultimately the four chambers of the heart. After the looping of the heart tube (E8.5), cardiac neural crest progenitors migrate from the dorsal neural tube to engulf the aortic arch arteries and contribute to vascular smooth muscle cells of the outflow tract (OFT) around E10.5. At the same time in mouse development, the proepicardial organ precursors contact the surface of the developing heart, give rise to the epicardial mantle (yellow) and contribute later to the coronary vasculature. In the fetal heart (E14), the chambers separate due to septation and are connected to the pulmonary trunk (PT) and aorta (Ao). Cranial (Cr)-caudal (Ca), right (R)-left (L), and dorsal (D)-ventral (V) axes are indicated. (B) Cardiac cell types that arise through the lineage diversification of the three embryonic precursor pools in the mouse heart. Whereas the contribution of the proepicardium to the smooth muscle cells of the coronary system and to the mesenchymal cells of the heart is well accepted, the origin of the endothelial lineage in the coronary vasculature is still controversial. AA, aortic arch; IVS, interventricular septum; LA, left atrium; LV, left ventricle; PhA, pharyngeal arches; PLA, primitive left atrium; PRA, primitive right atrium; RA, right atrium; RV, right ventricle.