Fig. 4. Wnt5a acts in the non-canonical pathway via Ror2 in lung development. (A,E) In wild-type lungs at E14, high levels of active β-catenin are detected in a patchy distribution in the buds of the most distal epithelium (black arrow, A and red arrows, inset A), whereas levels in the Wnt5a-mis/overexpressed lung are decreased (black arrow, E and red arrows, inset E). Active β-catenin is expressed in large interstitial vessels in wild type (red arrowheads, A) but is not detected in RCAS-Wnt5a-infected lungs (red arrowheads, E). (B-D,F-H) Explants grown for 5 days in organ culture demonstrate complex budding and overall organ growth in wild type (B), but lungs cultured after infection with RCAS-Wnt5a are hypoplastic with airway budding disarray and simplification (F). Treatment with the recombinant Dickkopf protein (Dkk1) impaired lung budding and growth in wild type (C) and did not rescue the Wnt5a phenotype (G, compare with F). The Wnt5a-mis/overexpressed hypoplastic phenotype (F) is partially rescued when embryos are co-infected with dnRor2 (H). Infection with the RCAS-dnRor2 construct alone showed dilated airways and mild overgrowth (hyperplasia; D).