Biophysics of lumen morphogenesis

Although lumen formation is a key feature of organogenesis, luminal compartments - formed through the secretion of fluid, ions and macromolecules by the cells, usually on the apical side - are often viewed as passive by-products of epithelial polarity. Here, we discuss how luminal fluids actively contribute to morphogenesis in metazoans through mechanical, hydraulic and electrochemical interactions with the surrounding epithelia and the extracellular matrix (ECM). We first outline the diversity of lumen architectures and summarize conserved mechanisms of lumen nucleation, fusion, folding and growth across metazoans. We then present the physical principles governing lumen morphogenesis, highlighting how hydrostatic and osmotic pressures, cortical tension and matrix mechanics interact to shape tissues. Furthermore, theoretical modeling and numerical simulations provide a quantitative framework for predicting phenotypes related to lumen shape, exploring the parameter space of hydraulic and active tissue mechanics variables, and linking molecular perturbations to emergent tissue geometries. Finally, we examine feedback loops whereby lumen-associated forces regulate junctional integrity, proliferation, differentiation and tissue patterning. Together, these concepts position luminal fluids as active regulators of lumen morphogenesis.