A vital issue in cell biology is how epithelial sheets provide a barrier while balancing cell growth and death, and withstand 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 consistent numbers. Rosenblatt and colleagues demonstrated that mechanical stretching stimulates epithelial cell division and characterized the stretch-sensitive Piezo1 channel as well as the downstream signaling that triggers cell division.
Mechanistically, they found that stretch triggers cells that are paused in the 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 channels, the type of mechanical force exerted controls the outcome: stretch induces cell division, whereas crowding induces extrusion.
Mechanical stretch triggers rapid epithelial cell division through Piezo1. Gudipaty SA, Lindblom J, Loftus PD, Redd MJ, Edes K, Davey CF, Krishnegowda V, Rosenblatt J. Nature. 2017 Mar;543(7643):118.