Unidirectional Shear Stress–Operated NOTCH/CXCR4 Molecular Switch Controls Semilunar Valve Maturation and Collagen Stratification

High-magnitude unidirectional laminar shear stress is transduced by endocardial cells, turning on a NOTCH1/CXCR4 molecular switch. This switch stops the valve mesenchymal growth program by inhibiting WNT/BMP. Simultaneously, it also orchestrates valve condensation, mesenchymal cell differentiation, and ECM (extracellular matrix) remodeling. Taken together, our findings identify a novel molecular switch controlled by local hemodynamic cues that directs valve maturation robustly in a side-specific manner.