Yap/Taz inhibit goblet cell fate to maintain lung epithelial homeostasis

Proper lung function relies on precisely balanced numbers of specialized epithelial cell types that work together and are maintained in homeostasis. We describe essential roles for the transcriptional regulators Yap and Taz, which are key effectors of Hippo pathway signaling, in maintaining lung epithelial homeostasis. We report that conditional deletion of Yap1/Yap and Wwtr1/Taz in the lung epithelium of adult mice results in severe defects with consequent animal lethality. Phenotypes associated with Yap/Taz deletion include alveolar defects and a striking development of goblet cell metaplasia throughout the airways. We performed gene expression analysis of wild type and Yap/Taz null primary mouse airway epithelial cells in order to define Yap/Taz controlled gene expression. Primary mouse airway epithelial cells were isolated from the tracheas of YapF/F; TazF/F; RosaCreER and YapF/F; TazF/F; No Cre mice. Cells were grown to confluence on collagen coated transwells in triplicate for each condition. All cells were cultured in the presence of 3uM 4-hydroxytamoxifen for 5 days in submerged mouse ALI expansion medium. RNA was extracted using the RNeasy Kit (Qiagen), subjected to Bioanalyzer quality assessment, and analyzed by Affymetrix Mouse Gene 2.0 ST array.