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From start to finish—a molecular link in wound repair

Sang-Uk Yun,V. Greco

Published 2022 in Science

ABSTRACT

Description p53 mediates epithelial cell migration and leader cell elimination during wound repair During epithelial wound repair, a subset of epithelial cells become “leaders” as the epithelial sheet collectively migrates to close the gap. These leader cells adopt distinct morphological characteristics and up-regulate migratory pathways (1, 2), but the molecular mechanism by which this subset emerges from an otherwise homogeneous population remained to be elucidated. On page 628 of this issue, Kozyrska et al. (3) find that leader cell behavior initiates with the activation of the tumor suppressor and transcription factor p53, which induces p21 expression and attendant cell cycle inhibition. Once the injury is resolved, leader cells are eliminated through p53-dependent crowding hypersensitivity. Classically, p53 becomes activated by cell stressors, including DNA damage, oncogenic expression, and hypoxia (4). In the case of mechanical disruption from wounding, p53 activation occurs through the stress kinase p38 (5). These newly found roles of p53 in leader cell emergence and elimination provide important insight into wound repair.

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