Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, AL 35294, USA.
School of Pharmaceutical Sciences and the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
Development. 2019 Jan 16;146(2):dev166454. doi: 10.1242/dev.166454.
Organ growth and tissue homeostasis rely on the proliferation and differentiation of progenitor cell populations. In the developing lung, localized expression maintains distal -expressing epithelial progenitors and promotes basal cell differentiation in the cartilaginous airways. Mesenchymal expression is induced by Wnt signaling but inhibited by Shh signaling, and epithelial Fgf10 signaling activates β-catenin signaling. The Hippo pathway is a well-conserved signaling cascade that regulates organ size and stem/progenitor cell behavior. Here, we show that Hippo signaling promotes lineage commitment of lung epithelial progenitors by curbing and β-catenin signaling. Our findings show that both inactivation of the Hippo pathway (nuclear Yap) or ablation of result in increased β-catenin and Fgf10 signaling, suggesting a cytoplasmic role for Yap in epithelial lineage commitment. We further demonstrate redundant and non-redundant functions for the two nuclear effectors of the Hippo pathway, Yap and Taz, during lung development.
组织生长和组织稳态依赖于祖细胞群体的增殖和分化。在发育中的肺中，局部表达维持远端表达的上皮祖细胞，并促进软骨气道中的基底细胞分化。间充质表达受 Wnt 信号诱导，但受 Shh 信号抑制，上皮 Fgf10 信号激活 β-连环蛋白信号。Hippo 通路是一种保守的信号级联，可调节器官大小和干细胞/祖细胞行为。在这里，我们表明 Hippo 信号通过抑制 和 β-连环蛋白信号来促进肺上皮祖细胞的谱系决定。我们的研究结果表明，Hippo 通路的失活（核 Yap）或 的缺失都会导致 β-连环蛋白和 Fgf10 信号的增加，这表明 Yap 在上皮谱系决定中具有细胞质作用。我们进一步证明了 Hippo 通路的两个核效应物 Yap 和 Taz 在肺发育过程中具有冗余和非冗余的功能。
