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Hippo/Yap signaling controls epithelial progenitor cell proliferation and
differentiation in the embryonic and adult lung
#MMPMID25480985
Lange AW
; Sridharan A
; Xu Y
; Stripp BR
; Perl AK
; Whitsett JA
J Mol Cell Biol
2015[Feb]; 7
(1
): 35-47
PMID25480985
show ga
The Hippo/Yap pathway is a well-conserved signaling cascade that regulates cell
proliferation and differentiation to control organ size and stem/progenitor cell
behavior. Following airway injury, Yap was dynamically regulated in regenerating
airway epithelial cells. To determine the role of Hippo signaling in the lung,
the mammalian Hippo kinases, Mst1 and Mst2, were deleted in epithelial cells of
the embryonic and mature mouse lung. Mst1/2 deletion in the fetal lung enhanced
proliferation and inhibited sacculation and epithelial cell differentiation. The
transcriptional inhibition of cell proliferation and activation of
differentiation during normal perinatal lung maturation were inversely regulated
following embryonic Mst1/2 deletion. Ablation of Mst1/2 from bronchiolar
epithelial cells in the adult lung caused airway hyperplasia and altered
differentiation. Inhibitory Yap phosphorylation was decreased and Yap nuclear
localization and transcriptional targets were increased after Mst1/2 deletion,
consistent with canonical Hippo/Yap signaling. YAP potentiated cell proliferation
and inhibited differentiation of human bronchial epithelial cells in vitro. Loss
of Mst1/2 and expression of YAP regulated transcriptional targets controlling
cell proliferation and differentiation, including Ajuba LIM protein. Ajuba was
required for the effects of YAP on cell proliferation in vitro. Hippo/Yap
signaling regulates Ajuba and controls proliferation and differentiation of lung
epithelial progenitor cells.
|*Signal Transduction
[MESH]
|Adaptor Proteins, Signal Transducing/genetics/*metabolism
[MESH]
free
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