Abstract
Epithelial sheets define organ architecture during development. Here, we employed an iterative multiscale computational modeling and quantitative experimental approach to decouple direct and indirect effects of actomyosin-generated forces, nuclear positioning, extracellular matrix, and cell-cell adhesion in shaping Drosophila wing imaginal discs. Basally generated actomyosin forces generate epithelial bending of the wing disc pouch. Surprisingly, acute pharmacological inhibition of ROCK-driven actomyosin contractility does not impact the maintenance of tissue height or curved shape. Computational simulations show that ECM tautness provides only a minor contribution to modulating tissue shape. Instead, passive ECM pre-strain serves to maintain the shape independent from actomyosin contractility. These results provide general insight into how the subcellular forces are generated and maintained within individual cells to induce tissue curvature. Thus, the results suggest an important design principle of separable contributions from ECM prestrain and actomyosin tension during epithelial organogenesis and homeostasis.
Highlights
Epithelial tissues are critical drivers of morphogenesis [1,2,3]
An iterative approach combining multiscale computational modelling and quantitative experimental approach was used to decouple direct and indirect roles of subcellular mechanical forces, nuclear positioning, and extracellular matrix in shaping the major axis of the wing pouch during the larval stage in fruit flies, which serves as a prototypical system for investigating epithelial morphogenesis
The research findings in this paper demonstrate that subcellular mechanical forces can effectively generate the curved tissue profile, while extracellular matrix is necessary for preserving the bent shape
Summary
Epithelial tissues are critical drivers of morphogenesis [1,2,3]. They serve as barriers between the environment and internal structures of organs. A predictive understanding of how organs regulate their shape at a given stage of the development remains elusive. This is partially because the roles of mechanical properties of components of cells and tissues during organ development are hard to quantify experimentally. Elucidating general design principles that can explain the overall mechanisms governing epithelial morphogenesis remains a key goal for characterizing multicellular systems [5,6,7]. Computational modeling approaches coupled to experimental studies are becoming powerful new tools to infer and test the basic design principles of epithelial morphogenesis
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