Gagliardi, Paolo ArmandoPaolo ArmandoGagliardiDobrzyński, MaciejMaciejDobrzyńskiJacques, Marc-Antoine Frédéric RoméoMarc-Antoine Frédéric RoméoJacquesDessauges, CoralieCoralieDessaugesEnder, Pascal PeterPascal PeterEnderBlum, YannickYannickBlumHughes, Robert MRobert MHughesCohen, Andrew RAndrew RCohenPertz, OlivierOlivierPertz2024-10-052024-10-052021-06-21https://boris-portal.unibe.ch/handle/20.500.12422/56882Cell death events continuously challenge epithelial barrier function yet are crucial to eliminate old or critically damaged cells. How such apoptotic events are spatio-temporally organized to maintain epithelial homeostasis remains unclear. We observe waves of extracellular-signal-regulated kinase (ERK) and AKT serine/threonine kinase (Akt) activity pulses that originate from apoptotic cells and propagate radially to healthy surrounding cells. This requires epidermal growth factor receptor (EGFR) and matrix metalloproteinase (MMP) signaling. At the single-cell level, ERK/Akt waves act as spatial survival signals that locally protect cells in the vicinity of the epithelial injury from apoptosis for a period of 3-4 h. At the cell population level, ERK/Akt waves maintain epithelial homeostasis (EH) in response to mild or intense environmental insults. Disruption of this spatial signaling system results in the inability of a model epithelial tissue to ensure barrier function in response to environmental insults.enAkt EGFR ERK apoptosis epithelial homeostasis fluorescent biosensors optogenetics signaling dynamics single-cell biology500 - Science::570 - Life sciences; biologyarticle10.48350/1567063408190810.1016/j.devcel.2021.05.007