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The embryonic heart forms as a linear tube consisting of myocardium and endocardium, separated by an abundant extracellular matrix (ECM) termed cardiac jelly.This vessel-like organ begins to contract in a peristaltic fashion resembling the contractile vessels that act as blood pumps in invertebrates.As the heart elongates and loops, specialized ventricular chambers are specified at the outer curvature flanked by endocardial cushions-exaggerated ECM swellings that act as primitive cardiac valves.During definitive valve formation, endocardial cells undergo local EMT,populating the cushion ECM with a fibrotic core, which is then remodeled into valve leaflets.The endocardium also plays an instructive role in development of heart chambers, during which prominent sponge-like myocardial protrusions termed trabeculae are elaborated on the luminal surface of the forming ventricles, serving to increase their surface area for oxygen and nutrient exchange, and contributing to force generation and conduction.However, the cellular and molecular mechanisms underlying trabeculation are poorly understood.Here, we propose a new model for cardiac chamber development and evolution based on the concept of endocardial cell sprouting and dynamic regulation of ECM synthesis and degradation.We have identified antagonistic roles for endocardial Neuregulin1/ErbB and Delta/Notch signaling pathways in control of sprouting, ECM flux and trabecular morphogenesis.Our data suggest that alternate cell fates arise within chamber endocardium, regulated by oscillations in Notch signaling, which leads to sprouting and the generation of local domains of matrix-rich and matrix-poor myocardium.We propose that local ECM composition and signaling controls cardiomyocyte cell behaviours and trabecular morphogenesis.Our model links the formation of specialized cardiac chambers, endocardial cushions and valves in primitive hearts to the evolutionary appearance and plasticity of a vascular endothelium.