During embryonic lung development, interacting signalling molecules made by the developing lung's outer mesothelium, mesenchyme and bronchial epithelium regulate lung growth and morphogenesis. Fibroblast growth factor 9 (FGF9),which is expressed in the mesothelium and epithelium during early lung development, and sonic hedgehog (SHH), which is expressed only in the epithelium, are required for both processes. On p. , David Ornitz and colleagues use Fgf9 loss-of-function and inducible gain-of-function mouse models to show that FGF9 and SHH signalling coordinate lung growth and development by regulating two distinct mesenchymal domains. They report that mesothelium-derived FGF9 signals stimulate proliferation in sub-mesothelial mesenchyme and that epithelium-derived FGF9 signals regulate SHH signalling in a distinct sub-epithelial mesenchyme domain; SHH signalling subsequently regulates cell proliferation and survival, and the expression of mesenchyme-to-epithelial signals. The researchers' report of distinct mesenchymal domains in the developing lung, which respond to different combinations of signalling molecules, is a novel finding that is of relevance to the study of other developing organs.
