Multiscale biophysical control of epithelial shape transitions during animal development.
The regulation of epithelial cell shape is fundamental to development, homeostasis and disease, and is intricately linked to tissue function. Epithelial morphology emerges from integration of biochemical and mechanical cues across multiple scales, from intrinsic cellular factors to tissue-wide forces. In this review we focus on the mechanical aspects of cell shape control and highlight the multi-scale regulation of epithelial cell shape that links (i) cell-intrinsic factors, such as cytoskeletal organization, contractility and growth, (ii) the local mechanical environment, including cell-matrix interactions and (iii) tissue-scale mechanics governing global morphogenesis. At the cellular level, contractility and growth generate stresses that interact with the surrounding microenvironment, shaped by the extracellular matrix. At the tissue level, large-scale stresses and boundary constraints from neighbouring tissues, bones or cuticles further shape epithelial morphology. Feedback across scales ensures robustness and adaptability of epithelial architecture. In this review, we synthesis recent insights into the mechanical control of epithelial cell-shape transitions and how intrinsic and extrinsic stresses integrate to drive morphogenesis. We also highlight how theoretical modelling frameworks are increasingly essential for disentangling the multiscale interplay of forces that govern epithelial architecture. This review aims to provide perspectives on how epithelial mechanics are coordinated by multiscale regulation and how they contribute to development, homeostasis and disease.