Apical Junctional Fluctuations Lead to Cell Flow while Maintaining Epithelial Integrity

Epithelial sheet integrity is robustly maintained during morphogenesis, which is essential to shape organs and embryos. While maintaining the planar monolayer in three-dimensional space, cells dynamically flow via rearranging their connections between each other. However, little is known about how cells maintain the plane sheet integrity in three-dimensional space and provide cell flow in the in-plane sheet. In this study, using a three-dimensional vertex model, we demonstrate that apical junctional fluctuations allow stable cell rearrangements while ensuring monolayer integrity. In addition to the fluctuations, direction-dependent contraction on the apical cell boundaries, which corresponds to forces from adherens junctions, induces cell flow in a definite direction. We compared the kinematic behaviors of this apical-force-driven cell flow with those of typical cell flow that is driven by forces generated on basal regions and revealed the characteristic differences between them. These differences can be used to distinguish the mechanism of epithelial cell flow observed in experiments, i.e., whether it is apical- or basal-force-driven. Our numerical simulations suggest that cells actively generate fluctuations and use them to regulate both epithelial integrity and plasticity during morphogenesis.