Maintaining Epithelial Barriers

A key issue in cell biology is how epithelial sheets can provide a barrier function while balancing cell growth and death, and the stretching forces that sheets experience in vivo. Among the questions raised is how the number of dying cells is matched by newly dividing cells to maintain constant numbers. Rosenblatt and colleagues demonstrated that mechanical stretching stimulates epithelial cell division and characterized the Piezo1 channel stretch sensing and the downstream signaling that triggers cell division. Mechanistically, they found that stretch triggers cells that are paused in early G2 phase to activate calcium-dependent phosphorylation of ERK1/2, thereby activating the cyclin B transcription that is necessary to drive cells into mitosis - causing cell division. Although both epithelial cell division and cell extrusion require Piezo1, the type of mechanical force controls the outcome: stretch induces cell division, whereas crowding induces extrusion.