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- Title
Epithelial Expression of YAP and TAZ Is Sequentially Required in Lung Development.
- Authors
Hideaki Isago; Akihisa Mitani; Yu Mikami; Masafumi Horie; Hirokazu Urushiyama; Ryuji Hamamoto; Yasuhiro Terasaki; Takahide Nagase
- Abstract
TAZ (transcriptional coactivator with PDZ-binding motif) and YAP (Yes-associated protein) are key molecules of the Hippo pathway. Recent studies revealed that these molecules are essential in lung development; however, the precise signaling cascade involving these molecules and the differences in their roles during lung development remain unknown. We aimed to investigate YAP and TAZ functions using lung epithelium-specific Taz and Yap conditional knockout mice. We generated lung epithelium-specific Taz and Yap conditional knockout mice and investigated the functions of YAP and TAZ in lung development. Selective TAZ deficiency in mouse lung epithelial cells resulted in abnormal alveolarization, which mimics lung emphysema, in adults, whereas YAP deficiency caused disruption of bronchial morphogenesis during the embryonic stage. We report that TAZ and YAP are sequentially expressed in the lung and that this could explain their different phenotypes. Furthermore, we report that YAP stimulates Shh (Sonic hedgehog) expression and regulates the FGF (fibroblast growth factor)-SHH feedback loop, thereby contributing to normal bronchial morphogenesis. We also found that TGF-b (transforming growth factor-b) stimulation induced Shh expression in the lung epithelial cells, and bothTAZand YAPare essential in this novel pathway. Our results provide a novel insight into the molecular mechanisms underlying lung development and contribute to a better understanding of the characteristics of TAZ and YAP.
- Subjects
LUNG development; GENE expression; KNOCKOUT mice; FIBROBLAST growth factors; MORPHOGENESIS
- Publication
American Journal of Respiratory Cell & Molecular Biology, 2020, Vol 62, Issue 2, p256
- ISSN
1044-1549
- Publication type
Article
- DOI
10.1165/rcmb.2019-0218OC