3D Cell Neighbour Dynamics in Growing Pseudostratified Epithelia

Abstract

During morphogenesis, epithelial sheets remodel into complex geometries. How cells dynamically organize their contact with neighbouring cells in these tightly packed tissues is poorly understood. We have used light-sheet microscopy of growing mouse embryonic lung explants, three-dimensional cell segmentation, and physical theory to unravel the principles behind 3D cell organization in growing pseudostratified epithelia. We find that cells have highly irregular 3D shapes and exhibit numerous neighbour intercalations along the apical-basal axis as well as over time. Despite the fluidic nature, the cell packing configurations follow fundamental relationships previously described for apical epithelial layers, i.e., Eulers formula, Lewis law, and Aboav-Weaires law, at all times and across the entire tissue thickness. This arrangement minimizes the lateral cell-cell surface energy for a given cross-sectional area variability, generated primarily by the distribution and movement of nuclei. We conclude that the complex 3D cell organization in growing epithelia emerges from simple physical principles.