During lung development, the secreted signalling molecule fibroblast growth factor 9 (FGF9) is expressed in both the mesothelium (the single layer of cells that envelopes the lungs) and the pulmonary epithelium (which gives rise to the proximal airways and terminal epithelial buds). Mesenchymal proliferation and epithelial branching are both reduced in Fgf9–/– embryos, which die at birth because of impaired lung development. Intriguingly, David Ornitz and colleagues now show that mesothelial- and epithelial-derived FGF9 have distinct functions during lung development in mouse (see ). Mesothelial-derived FGF9 and mesenchymal WNT2A, they report, are required to maintain the mesenchymal FGF-WNT/β-catenin signalling pathway that is responsible for mesenchymal growth. By contrast, epithelial-derived FGF9 primarily affects epithelial branching, probably through regulation of BMP4 signalling. The researchers also show that epithelial and mesothelial FGF9 and mesenchymal β-catenin suppress the expression of the BMP4 antagonist Noggin in lung mesenchyme, thereby providing a mechanism for coupling mesenchymal and epithelial proliferation during lung development.
