During heart development, the endothelial-like endocardial and muscular myocardial layers of the heart derive from a common progenitor and differentiate in close proximity. Previous research has shown that signalling between the endocardium and myocardium is crucial at later stages of cardiac development. However, studying the interactions between these cells in the early stages of cardiogenesis has been a challenge. Now, H. Scott Baldwin and colleagues have developed an in vitro embryoid-body model to investigate whether the endocardium is required for myocardium development. The authors use a diphtheria toxin ablation system to specifically remove NFATc1-expressing endocardial cells during the initial stages of cardiac development. They show that, under these conditions, the function, differentiation and maturation of cardiomyocytes are attenuated, which is indicated by a loss of beating cells and expression of key marker genes, such as Nkx2.5. Analyses of the endocardial transcriptome reveals expression of several growth factors, including Bmp2, which can partially rescue the effects of endocardial ablation. As well as developing a useful model for studying these interactions, these data provide the first direct evidence for a crucial role of the endocardium on the subsequent development of the myocardium through paracrine signalling.