Focal Sources of FGF-10 Promote the Buckling Morphogenesis of the Embryonic Airway Epithelium

During airway branching morphogenesis, focal regions of FGF-10 expression in the pulmonary mesenchyme are thought to provide a local guidance cue, which promotes chemotactically the directional outgrowth of the airway epithelium. Here, however, we show that an ectopic source of FGF-10 induces epithelial buckling morphogenesis and the formation of multiple new supernumerary buds. FGF-10-induced budding can be modulated by altered epithelial tension and luminal fluid pressure. Increased tension suppresses the formation of ectopic branches, while a collapse of the embryonic airway promotes more expansive buckling and additional FGF-10-induced supernumerary buds. Our results indicate that a focal source of FGF-10 can promote epithelial buckling and suggest that the overall branching pattern cannot be explained entirely by the templated expression of FGF-10. Both FGF-10-mediated cell behaviors and exogenous mechanical forces must be integrated to properly shape the bronchial tree.