Heart valves form from endocardial cushions during late development to prevent retrograde blood flow. Because cardiac valve and heart septation defects are common human congenital disorders, it is crucially important to understand their aetiology. On p. , Beis and colleagues shed light on heart valve formation through a combination of approaches in zebrafish. From their studies, they identify a new step in early valve formation that is characterised by changes in the shape and adhesion-marker profile of endocardial cells in the atrioventricular canal(AVC). These changes fail in sih mutants whose hearts do not contract, indicating that they depend on the heart's mechanical function. They also depend on Notch signalling, which the authors show restricts this differentiation program to the correct cells in the AVC. Further insights are likely to arise from the large-scale genetic screen also reported here, which provides a valuable resource for the further dissection of this clinically important developmental process.
