Fig. 6.

Working hypothesis. Schematic drawing of how NPAS3 might function in epithelial and mesenchymal cells in developing lungs. NPAS3 regulates transcription of Shh and Fgf9, which would lead to increased SHH signaling via PATCHED with activation of Gli2 and the cascade of genes activated by SHH signaling. NPAS3 activation of FGF signaling includes FGF9 and FGF10, which reciprocally activate both epithelial and mesenchymal cells. FGFR2 signaling is inhibited by SPRY2, but NPAS3 represses Spry2 expression, and thus facilitates FGF signaling during lung development.