Loss of epithelial Gpr177 in the Shh-Cre;Gpr177loxp/loxp (Gpr177Δ/Δ) mutants leads to reduced Wnt signaling and severe pulmonary hemorrhage. (A,B) Deletion of epithelial Gpr177 reduces canonical Wnt signaling in both the epithelium and mesenchyme of the E12.5 lungs, as shown by the Axin2-lacZ allele. (C) Whole-mount microscopy shows reduced branching in the left lobe of E12.5 mutant lung. Arrowheads indicate lateral secondary branches in the normal lung. (D) Gpr177 deletion leads to hypoplastic lung with severe hemorrhage. (E) Hematoxylin and Eosin staining shows interstitial space in the mutant lung is filled with blood cells. ep, epithelium; me, mesenchyme; lu, lung; st, stomach. Scale bars: 50 μm.