As the heart is the first organ to form during mammalian embryogen- esis, the decisions to commit towards a cardiac cell fate are taken early in the developmental process. Studies including explant cultures, mouse/chick graft, chick/quail graft, and cell fate mapping experiments
demonstrated that cardiac precursor cells are found before gastrula-tion and are located in the lateral posterior epiblast in pre-streak embryos13 (Figure 1A). Gastrulation, the morphogenetic process that leads to the formation of the three germ layers (ectoderm, meso- derm, and endoderm) begins with the appearance of the primitive streak (PS). A subset of epiblast cells then moves as a sheet to the PS, and undergoes epithelial-to-mesenchymal transition (EMT), in order to ingress and transiently forms the mesendoderm.In fish and amphibians, the mesendoderm represents an intermedi-ate germ layer from which the endoderm and mesoderm subsequent-ly segregate. In an amniote, the prospective ‘mesendodermal’ cells ingress through the PS to reach their correct topographical positions during gastrulation. The first cells to ingress give rise to the ‘primitive endoderm’ [visceral endoderm (VE) in mammals equivalent to hypo- blast in chick].14 Then, the second wave of ingressing cells gives rise to extraem extraembryonic and embryonic mesodermal cells. GATA factors 4,5,6