FIGURE 1.

A Wnt7b-Fgf10 epithelial-mesenchymal crosstalk maintains distal epithelial progenitors during lung development and becomes reactivated in the adult lung to regenerate injured airway epithelium. (A) During the branching stage of lung development, Fgf10 is expressed by mesenchymal progenitor cells, which depends on Wnt/β-catenin signaling, and acts on the distal epithelium to induce Bmp4 and Sox9 expression to keep them in an undifferentiated state. As the epithelial tube grows toward the Fgf10 source, Sox9 + progenitors acquire more proximal positions, switch on Sox2 expression and acquire bronchial epithelial fate. Simultaneously, distal Fgf10-expressing airway smooth muscle (ASMC) progenitors encounter epithelial Bmp4 and Shh (not shown) causing them to stop expressing Fgf10 and differentiate into mature ASMCs as they relocate proximally. (B) In the adult, basal stem cells (BSCs) generate their own Fgf10-expressing niche mediated by Yap-Wnt7b, and their maintenance is critically dependent on Fgf10-Fgfr2b signaling. The non-cartilaginous airway epithelium is kept quiescent during homeostasis, by active Integrin-linked kinase (Ilk)-Hippo signaling, which prevents Fgf10 expression in ASMCs. In response to injury, surviving epithelial cells spread out, leading to a destabilization of Merlin and inactivation (dephosphorylation) of Hippo kinases Mst1/2. This increases nuclear Yap in spreading epithelial cells causing these cells to secrete Wnt7b. Epithelial-derived Wnt7b then acts on ASMCs to induce Fgf10 expression, which is required for epithelial regeneration. Solid cell borders represent lineage labels to follow the fate of epithelial cells in response to injury.