Fig. 5. Mechanism of Wnt7b action in mouse lung development. (A) ISH showing loss of canonical Wnt targets in mesenchyme and endoderm of Wnt7b mutant lungs. Dotted lines encircle epithelium. Arrowheads point to periendodermal mesenchyme. (B) E12.5 whole-mount ISH of Axin2 and Lef1 in cultured wild-type lungs. Wnt signaling is decreased with the addition of Dkk1 (left) and enhanced by lithium (right) when compared with control cultures (middle). In lithium-treated lungs, mesenchymal staining of the canonical targets has expanded. (C) Axin2 expression in mesenchyme cultured alone and in mesenchyme recombined with epithelium, showing that mesenchymal Axin2 expression requires endoderm induction. (D) Lithium rescues Lef1 expression in E12.5 mutant lungs when compared with Wnt7b mutant lungs cultured without lithium. (E) Epithelial Wnt7b activates a canonical pathway in neighboring mesenchyme. (F) Bmp4 and Id2 expression are coincident on serial sections of E14.5 wild-type lung (left). Expression of epithelial Bmp4 and Id2 are decreased in mutant lungs (middle and right). (G) Lithium induces ectopic Id2 expression in cultured E12.5 wild-type lungs. (H) Wnt7b induces Bmp4 and Id2 production in endoderm tip cells. (I) Wnt7b coordinately activates autocrine and paracrine signaling cascades to increase cell replication.