Bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) signals are involved in the induction of the proepicardial organ (PE). In chick embryos, strong BMP signaling promotes myocardial differentiation of the precursor pool of the splanchnic mesoderm through p-Smad1/5/8, whereas weak BMP signaling stimulates PE formation. FGF signaling negatively regulates BMP signaling in the PE region via p-Erk1/2 to promote PE formation, although whether FGF signaling is required for the induction or maintained expression of PE-specific genes, such as Tbx18, is controversial (van Wijk et al. 2009; Torlopp et al. 2010). In contrast, blocking BMP signaling in zebrafish embryos reduces tbx18 and tcf21 expression and PE specification, whereas elevated bmp2b expression before PE formation induces ectopic expression of tbx18 (Liu and Stainier 2010). A, Atrium; V, ventricle; AVJ, atrioventricular junction; SV, sinus venosus.