Fig. 1. FGF9 induces mesenchymal and epithelial expansion in vitro. (A-C) Increased distal mesenchyme adjacent to an FGF9 bead (red line, B) and decreased distal mesenchyme adjacent to an FGF10 bead (red line, C) compared with a BSA bead (red line, A) in E11.5 lung organ cultures incubated for 24 hours. (D-F) After 48 hours, epithelial luminal expansion occurs in cultures incubated with either FGF9 (E) or FGF10 (F) beads compared with control (D). Mesenchymal expansion at 48 hours (red lines, D-F) remained higher in explants treated with FGF9 (red lines, A-C). Arrow in E indicates a narrow band of mesenchyme between the epithelium and the FGF9 bead, not evident in FGF10 bead-treated cultures (F). (G) lacZ staining for the Rosa26 reporter demonstrates Dermo1-Cre activity throughout E13.5 lung mesenchyme. (H-K) Decreased lung size in mesenchymal Fgfr conditional knockouts at E17.5. Dermo1-Cre;Fgfr1^+/–;Fgfr2^+/– (H) and Dermo1-Cre;Fgfr1^–/–;Fgfr2^+/– (not shown) lungs exhibit wild-type size and morphology. Dermo1-Cre;Fgfr1^+/–;Fgfr2^–/– lungs (I) are moderately hypoplastic, and Dermo1-Cre;Fgfr1^–/–;Fgfr2^–/– lungs are severely hypoplastic with variable morphology (J,K). H-K are left lung lobes.