Fig. 4. Foxf1 is a target for Sonic hedgehog signaling in lung. (A-C) Gene expression in E11.5 mouse lung examined by whole-mount in situ hybridization. Shh (A) is expressed throughout the lung epithelium, but the highest expression level is restricted to distal epithelium in the bulbous ends of the buds. Ptch (B), encoding the Shh receptor, and Foxf1 (C) are both expressed in mesenchyme adjacent to lung epithelium. The expression patterns mirror the distribution of Shh, with low levels along the proximal tubular epithelium and higher levels distally. (D-G) Exogenous Shh activates Foxf1. COS-7 cells transfected to secrete Shh (D,F) or control COS-7 cells (E,G) were grafted into the mesenchyme (location of grafts indicated by white stars) of wild-type lung explants, which were then cultivated for 24 hours. The expression of Ptch (D,E) and Foxf1 (F,G) were examined by whole-mount in situ hybridization. The mesenchyme immediately adjacent to the Shh-producing cells express elevated levels of both Ptch (D) and Foxf1 (F), whereas no change is induced by control cells (E,G).