Coordination between Cell Motility and Cell Cycle Progression in Keratinocyte Sheets via Cell-Cell Adhesion and Rac1

Regulations of cell motility and proliferation are essential for epithelial development and homeostasis. However, it is not fully understood how these cellular activities are coordinated in epithelial collectives. In this study, we find that keratinocyte sheets exhibit time-dependent coordination of collective cell movement and cell cycle progression after seeding cells. Cell movement and cell cycle progression are coordinately promoted by Rac1 in the "early phase" (earlier than ∼30 h after seeding cells), which is not abrogated by increasing the initial cell density to a saturated level. The Rac1 activity is gradually attenuated in the "late phase" (later than ∼30 h after seeding cells), leading to arrests in cell motility and cell cycle. Intact adherens junctions are required for normal coordination between cell movement and cell cycle progression in both early and late phases. Our results unveil a novel basis for integrating motile and proliferative behaviors of epithelial collectives.