Abstract
ABSTRACTSize 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.
Highlights
The size of biological tissues is determined by well-coordinated multicellular actions, and its control is essential for various biological processes, including embryonic development, regeneration, and tissue homeostasis
Cell division orientation is unbiased within the monolayer of developing epididymal tubes Because cell division orientation is known as a key determinant for the morphogenesis of developing tubes (Fischer et al, 2006; Tang et al, 2011), we examined cell division orientation in mouse epididymal tubes at E15.5 and E16.5
We evaluated whether cell cycle entry into M phase in the developing epididymal tubes was inhibited by mitomycin C (MMC) treatment at a concentration of 3 μM in explant cultures and found that the cell division was completely inhibited by 18 h after the treatment (Fig. 3H)
Summary
The size of biological tissues is determined by well-coordinated multicellular actions, and its control is essential for various biological processes, including embryonic development, regeneration, and tissue homeostasis. An underlying principle of this communication is cellular sensing of and responses to mechanical forces Collective activation of a mechano-response in individual cells is considered to underlie the multicellular actions responsible for maintaining tissue size (Hannezo and Heisenberg, 2019)
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