Cell proliferation maintains cell area polydispersity in the growing fruit fly wing epithelium

Abstract

Developing epithelial tissues coordinate cell proliferation and mechanical forces to achieve proper size and shape. As epithelial cells tightly adhere together to form the confluent tissue, the distribution of cell areas significantly influences possible patterns of cellular packing and thereby also the mechanics of the epithelium. Therefore, it is important to understand the origin of cell area heterogeneity in developing tissues and, if possible, how to control it. Previous models of cell growth and division have been successful in accounting for experimentally observed area distributions in cultured cells and bacterial colonies, but developing tissues present additional complexity due to self-organized patterns of mechanical stresses that guide morphogenesis. Here, we address this challenge focusing on the D. melanogaster wing disc epithelium. We consider a simple model that couples cell cycle dynamics to tissue mechanics. From time-lapse imaging of the cellular network, we extract all model parameters - cell growth rates, division rates, and mechanical fluctuations - revealing that they all depend on cell size. With these independently measured parameters, our model quantitatively reproduces the observed cell area distribution without any fitting parameters and further predicts tissue pressure gradients, in quantitative agreement with previously published data. Importantly, we find that cell proliferation accounts for 85% of cell area variance, establishing it as the dominant source of packing disorder that influences tissue mechanics and organization.