YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis.
Branching morphogenesis is a fundamental program for tissue patterning. We show that active YAP, a key mediator of Hippo signaling, is distributed throughout the murine lung epithelium and loss of epithelial YAP severely disrupts branching. Failure to branch is restricted to regions where YAP activity is removed. This suggests that YAP controls local epithelial cell properties. In support of this model, mechanical force production is compromised and cell proliferation is reduced inYapmutant lungs. We propose that defective force generation and insufficient epithelial cell number underlie the branching defects. Through genomic analysis, we also uncovered a feedback control of pMLC levels, which is critical for mechanical force production, likely through the direct induction of multiple regulators by YAP. Our work provides a molecular pathway that could control epithelial cell properties required for proper morphogenetic movement and pattern formation.
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
Chuwen
C
Lin
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
Erica
E
Yao
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
Kuan
K
Zhang
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
Xuan
X
Jiang
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
Stacey
S
Croll
Department of Physiology, Howard Hughes Medical institute, University of California, San Francisco, San Francisco, United States.
Katherine
0000-0002-4200-3870
K
Thompson-Peer
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
Pao-Tien
0000-0002-8961-8653
PT
Chuang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000502:physiology*; D055786:Gene Knockout Techniques; D008168:Lung / Q000196:embryology*; D051379:Mice; D009024:Morphogenesis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse
Hippo signaling; YAP; actomyosin; developmental biology; lung branching; mechanical force; mouse; stem cells