YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis

Lin, Chuwen; Yao, Erica; Zhang, Kuan; Jiang, Xuan; Croll, Stacey; Thompson-Peer, Katherine L.; Chuang, Pao-Tien

doi:10.7554/elife.21130

Cited by 112 publications

(128 citation statements)

References 60 publications

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“…However, Yap target genes are not restricted to these categories, being also found to be quite diverse and context‐dependent, as demonstrated by the Yap regulation of Ajuba , Ankrd1 , Areg , and SGK1 (Dupont et al, ; Lange et al, ; Yoo, Kim, Chung, Hwang, & Lim, ; J. Zhang et al, ). For example, while Sox9 is upregulated by Yap in hepatocytes, there is no evidence that in the developing lung epithelium Yap gain or loss of function has any obvious impact in Sox9 expression (Lin et al, ; Mahoney et al, ; van Soldt et al, ; Yimlamai et al, ). Thus, a central question revolves around the ability of Yap to induce gene expression in a context‐dependent manner.…”

Section: Transcriptional Roles Of Yap/tazmentioning

confidence: 99%

“…Disruption of Yap in the lung epithelium of Shh Cre ; Yap f/f mice show that, although not required for specification of the distal progenitors, Yap is crucial to form the Sox2+ epithelial compartment. Indeed, analysis of Yap‐deficient lungs in vivo reveals a markedly truncated Sox2+ domain (airways) associated with large cyst‐like dilated Sox9+ distal buds (Lin et al, ; Mahoney et al, ; van Soldt et al, ). Interestingly, there is evidence suggesting that the Yap effects in Sox2 specification and airway morphogenesis are not fully interdependent.…”

Section: Transcriptional Roles Of Yap/tazmentioning

confidence: 99%

“…Here, Yap induces Arhgap18 , a Rho activator, leading to actin accumulation, increased actomyosin tension and Fibronectin accumulation (Porazinski et al, ). Another example comes from lung development, where Yap induces MLCK‐mediated cytoskeletal tension in epithelial cells of the distal bud tips to ensure normal branching morphogenesis through the induction of Ahrgef17 , a Rho inhibitor (Lin et al, ). Thus Yap induces both Rho activators and inhibitors, a striking paradox that might depend on context.…”

Section: Hippo In Cell Fate Commitment and Maturation: Cytoplasmic Sementioning

confidence: 99%

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Hippo‐Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior

Soldt

Cardoso

2019

WIREs Developmental Biology

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The Hippo pathway has emerged as a crucial integrator of signals in biological events from development to adulthood and in diseases. Although extensively studied in Drosophila and in cell cultures, major gaps of knowledge still remain on how this pathway functions in mammalian systems. The pathway consists of a growing number of components, including core kinases and adaptor proteins, which control the subcellular localization of the transcriptional co‐activators Yap and Taz through phosphorylation of serines at key sites. When localized to the nucleus, Yap/Taz interact with TEAD transcription factors to induce transcriptional programs of proliferation, stemness, and growth. In the cytoplasm, Yap/Taz interact with multiple pathways to regulate a variety of cellular functions or are targeted for degradation. The Hippo pathway receives cues from diverse intracellular and extracellular inputs, including growth factor and integrin signaling, polarity complexes, and cell–cell junctions. This review highlights the mechanisms of regulation of Yap/Taz nucleocytoplasmic shuttling and their implications for epithelial cell behavior using the lung as an intriguing example of this paradigm. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms Signaling Pathways > Cell Fate Signaling Establishment of Spatial and Temporal Patterns > Cytoplasmic Localization

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Section: Transcriptional Roles Of Yap/tazmentioning

confidence: 99%

Section: Transcriptional Roles Of Yap/tazmentioning

confidence: 99%

Section: Hippo In Cell Fate Commitment and Maturation: Cytoplasmic Sementioning

confidence: 99%

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Hippo‐Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior

Soldt

Cardoso

2019

WIREs Developmental Biology

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“…In cell collectives YAP/TAZ translocate to the nuclei of leader cells to regulate endothelial cell migration (Lin et al, 2017;Yu and Guan, 2013;Zhang et al, 2015;Mason et al, 2019;Neto et al, 2018)(and Suppl. Fig.…”

Section: Endothelial Dlc1 Controls Cell Orientation and Directed Migrmentioning

confidence: 99%

DLC1 is a direct target of activated YAP/TAZ that drives collective migration and sprouting angiogenesis

Stoel

Schimmel

Nawaz

et al. 2019

Preprint

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YAP/TAZ signaling is crucial for sprouting angiogenesis and vascular homeostasis through the regulation of endothelial remodeling. Thus far the underlying molecular mechanisms that explain how YAP/TAZ control the vasculature remain unclear. We here identify Deleted-in-Liver-Cancer-1 (DLC1) as a direct transcriptional target of the activated YAP/TAZ-TEAD complex in the endothelium. Substrate stiffening and VEGF stimuli promote the endothelial expression of DLC1. DLC1 expression is dependent on the presence of YAP and TAZ, and constitutive activation of YAP efficiently promotes expression of DLC1. We show that DLC1 limits F-actin fiber formation, integrin-based focal adhesion lifetime and integrin-mediated traction forces. Depletion of endothelial DLC1 strongly perturbs cell polarization in directed collective migration and inhibits the formation of angiogenic sprouts. Importantly, the inability of YAP-depleted endothelial cells to collectively migrate and form angiogenic sprouts can be rescued by ectopic expression of DLC1. Together, these findings reveal that DLC1 fills a hitherto missing link between YAP/TAZ signaling and endothelial dynamics during angiogenesis.

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“…These data suggest that YAP/TAZ mediate feedback control of cytoskeletal and focal adhesion dynamics through the Rho-ROCK-myosin II pathway. We performed a meta-analysis of previously published ChIP-seq and gene expression data and identified SNF-like kinase 2 (NUAK2), Rho GTPase activating protein 28 (ARHGAP28), and ARHGAP29 as YAP/TAZdependent target genes [34][35][36][37] . We confirmed that YAP/TAZ regulate these putative targets by PCR of ECFC mRNA 1 hour after initiation of the wound assay.…”

Section: Yap/taz Regulate Nuak2 To Control Cytoskeletal Polymerizationmentioning

confidence: 99%

Persistent cell motility requires transcriptional feedback of cytoskeletal — focal adhesion equilibrium by YAP/TAZ

Mason

Dawahare

Nguyen

et al. 2018

Preprint

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Cell migration initiates by traction generation through reciprocal actomyosin tension and focal adhesion reinforcement, but continued motility requires adaptive cytoskeletal remodeling and adhesion release. Here, we asked whether de novo gene expression contributes to this cytoskeletal feedback. We found that global inhibition of transcription or translation does not impair initial cell polarization or migration initiation, but causes eventual migratory arrest through excessive cytoskeletal tension and over-maturation of focal adhesions, tethering cells to their matrix. The transcriptional co-activators YAP and TAZ mediate this feedback response, modulating cell mechanics by limiting cytoskeletal and focal adhesion maturation to enable persistent cell motility and 3D vasculogenesis. Motile arrest after YAP/TAZ ablation was partially rescued by depletion of the YAP/TAZ-dependent myosin phosphatase regulator, NUAK2, or by inhibition of Rho-ROCK-myosin II. Together, these data establish a transcriptional feedback axis necessary to maintain a responsive cytoskeletal equilibrium and persistent migration. Main Text

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YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis

Cited by 112 publications

References 60 publications

Hippo‐Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior

Hippo‐Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior

DLC1 is a direct target of activated YAP/TAZ that drives collective migration and sprouting angiogenesis

Persistent cell motility requires transcriptional feedback of cytoskeletal — focal adhesion equilibrium by YAP/TAZ

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