Abstract
Cell 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. Such a propagation 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 hours. At the cell population level, ERK/Akt waves maintain epithelial homeostasis (EH) in response to mild or intense insults. Disruption of this spatial signaling system results in the inability of a model epithelial tissue to ensure barrier function in response to cellular stress.
Competing Interest Statement
The authors have declared no competing interest.