Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

The coordination of cell proliferation and migration in growing tissues is crucial in development and regeneration but remains poorly understood. Here, we nd that, while expanding with an edge speed independent of initial conditions, millimeter-scale epithelial monolayers exhibit internal patterns of proliferation and migration that depend not on the current but on the initial tissue size, indicating memory e ects. Speci cally, the core of large tissues becomes very dense, almost quiescent, and ceases cell-cycle progression. In contrast, initially-smaller tissues develop a local minimum of cell density and a tissue-spanning vortex. To explain vortex formation, we propose an active polar uid model with a feedback between cell polarization and tissue ow. Taken together, our ndings suggest that expanding epithelia decouple their internal and edge regions, which enables robust expansion dynamics despite the presence of size-and history-dependent patterns in the tissue interior.