Pattern formation of an epithelial tubule by mechanical instability during epididymal development

A single epithelial tubule undergoes morphogenesis to form a functional shape during the development of internal organs; however, the mechanical processes that are directed by the molecular signals regulating tubular morphogenesis are poorly understood. Here, axial tubular buckling triggered by cell proliferation is shown to drive the morphogenesis of murine epididymal tubules through mechanical interactions between the developing epithelial tubule and its surrounding tissues. Through immunofluorescence labeling and mathematical modeling, epididymal tubule shape formation is found to depend on two factors: cell proliferation area in the tubule and mechanical resistance from the tissues surrounding the tubule. Moreover, experimental perturbations of these two factors alter the shape of the epididymal tubule as predicted by the mathematical model, suggesting that the shape of the epididymal tubule spontaneously emerges through mechanical coupling between developing tissues instead of by growing according to a predetermined fate.