Polarized Cellular Mechanoresponse System for Maintaining Radial Size in Developing Epithelial Tubes

Abstract

Size control in biological tissues involves multicellular communication via mechanical forces during development. Although fundamental cellular behaviours in response to mechanical stimuli underlie size maintenance during morphogenetic processes, the mechanisms underpinning the cellular mechano-response system that maintains size along an axis of a polarized tissue remain elusive. Here, we show how the diameter of an epithelial tube is maintained during murine epididymal development by combining quantitative imaging, mechanical perturbation and mathematical modelling. We found that epithelial cells counteract compressive forces caused by cell division exclusively along the circumferential axis of the tube to produce polarized contractile forces, eventually leading to an oriented cell rearrangement. Moreover, a mathematical model that includes the polarized mechano-responsive regime explains how the diameter of proliferating tubes is maintained. Our findings pave the way for an improved understanding of the cellular response to mechanical forces that involves collective multicellular behaviours for organizing diverse tissue morphologies.