YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development

Neto, Filipa; Klaus-Bergmann, Alexandra; Ong, Yu Ting; Alt, Silvanus; Vion, Anne-Clémence; Szymborska, Anna; Carvalho, Joana Rita; Hollfinger, Irene; Bartels-Klein, Eireen; Franco, Cláudio A.; Potente, Michael; Gerhardt, Holger

doi:10.7554/elife.31037

Cited by 204 publications

(229 citation statements)

References 58 publications

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“…Highly distended lacteals reacted with a limited proliferative response (Appendix Fig S5), which may have been caused by increased mechanical stretch due to obstruction of the mesenteric collectors. Such mechano‐stimulation of LEC proliferation has been shown to be VEGFR‐3‐mediated and independent of VEGF‐C levels, but dependent on YAP/TAZ nuclear localization (Planas‐Paz et al , ; Neto et al , ). Supporting the assumption that intestinal defects were caused by the demise of mesenteric collectors, mesenteric defects temporally preceded fragmentation of lacteals (Figs EV3 and EV4).…”

Section: Discussionmentioning

confidence: 99%

“…Mesenteric LECs that had lost VEGFR‐3 surface expression, but upregulated VEGFR‐2, which has previously been reported for retinal blood vessels (Zarkada et al , ). Proliferation of ECs in response to VEGF‐A is independent of YAP/TAZ (Neto et al , ). Still YAP/TAZ can become activated downstream of VEGF‐A or in response to mechanic signals and then provide the optimal transcriptional program for VEGF‐driven endothelial proliferation (Wang et al , ; Neto et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…Proliferation of ECs in response to VEGF-A is independent of YAP/TAZ (Neto et al, 2018). Still YAP/TAZ can become activated downstream of VEGF-A or in response to mechanic signals and then provide the optimal transcriptional program for VEGF-driven endothelial proliferation (Wang et al, 2017;Neto et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Distinct roles of VE ‐cadherin for development and maintenance of specific lymph vessel beds

et al. 2018

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Endothelial cells line blood and lymphatic vessels and form intercellular junctions, which preserve vessel structure and integrity. The vascular endothelial cadherin, VE‐cadherin, mediates endothelial adhesion and is indispensible for blood vessel development and permeability regulation. However, its requirement for lymphatic vessels has not been addressed. During development, VE‐cadherin deletion in lymphatic endothelial cells resulted in abortive lymphangiogenesis, edema, and prenatal death. Unexpectedly, inducible postnatal or adult deletion elicited vessel bed‐specific responses. Mature dermal lymph vessels resisted VE‐cadherin loss and maintained button junctions, which was associated with an upregulation of junctional molecules. Very different, mesenteric lymphatic collectors deteriorated and formed a strongly hyperplastic layer of lymphatic endothelial cells on the mesothelium. This massive hyperproliferation may have been favored by high mesenteric VEGF‐C expression and was associated with VEGFR‐3 phosphorylation and upregulation of the transcriptional activator TAZ. Finally, intestinal lacteals fragmented into cysts or became highly distended possibly as a consequence of the mesenteric defects. Taken together, we demonstrate here the importance of VE‐cadherin for lymphatic vessel development and maintenance, which is however remarkably vessel bed‐specific.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Distinct roles of VE ‐cadherin for development and maintenance of specific lymph vessel beds

et al. 2018

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“…Cytoplasmic localization of YAP is primarily governed by its phosphorylation; thus, dephosphorylated YAP translocates into the nucleus, where it binds transcriptional factors, triggering the expression of target genes while limiting its own cytoplasmic sequestration and subsequent degradation (Zhao et al, 2007). An increasing number of studies have shown that VEGF induces YAP activation via promoting its nuclear translocation and the activity of YAP is required for transducing the VEGF signal into a specific transcriptional program, needed for a full angiogenesis response (Neto et al, 2018). Deletion of YAP is responsible for the impaired cytoskeleton rearrangements and VEGFR2 trafficking to the membrane in ECs, leading to compromised angiogenesis (Wang et al, 2017).…”

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confidence: 99%

Gambogic acid impairs tumor angiogenesis by targeting YAP/STAT3 signaling axis

Wan

Zhang

Wang

et al. 2019

Phytotherapy Research

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Angiogenesis is central to a wide range of physiological and pathological processes including wound healing, macular degeneration, and cancer. Excessive or inappropriate vascular supply of tumors is one of the main targets for cancer therapy. Recently, critical and selective transcriptional factors such as yes‐associated protein (YAP) that control the expression of angiogenesis factors have gained increasing attention in antiangiogenic therapy. In this study, we have identified and characterized a novel inhibitor of YAP, gambogic acid (GA), which exerted striking antiangiogenic effects both in vitro and in vivo. We demonstrated that GA remarkably inhibited a variety of vascular endothelial growth factor‐induced angiogenesis processes including proliferation, migration, sprouting, and tube formation of endothelial cells in vitro. In addition, GA resulted in decreased neo‐vessel formation in Matrigel plugs of mice and chick chorioallantoic membrane. More importantly, we showed that GA limited tumor growth via preventing tumor angiogenesis and vascular maturation. Further mechanistic studies illustrated that GA directly targeted YAP/STAT3 signaling axis, which is critical for the transcriptional regulation of a series of angiogenic factors. Taken together, these preclinical findings suggest that GA significantly repressed tumor angiogenesis and may serve as a promising drug candidate against cancer.

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“…Fluorescence immunostaining with isolectin B4 (IB4) and anti-GFAP showed accordant localization of endothelium and astrocytes, respectively, from P3 to P21 ( Figure S1A,B). YAP, a transcriptional coactivator in Hippo signalling, is an important regulator of angiogenesis, 11 as well as retinal vascular development. However, the effect of YAP on the relationship between astrocyte growth and blood vessels needs to be elucidated.…”

Section: Yap Is Critical For Retinal Vessel Developmentmentioning

confidence: 99%

Retinal blood vessel‐origin yes‐associated protein (YAP) governs astrocytic maturation via leukaemia inhibitory factor (LIF)

Yuan

Chen

et al. 2020

Cell Proliferation

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Objectives To testify that endothelial cells (ECs) induce astrocyte maturation by leukaemia inhibitory factor (LIF) secretion. Materials and Methods In vivo experiments, mice bearing floxed alleles of YAP were crossed with mice expressing a Cre recombinase driven by the endothelial Tek promoter (Tek‐Cre) to finally obtain the following three genotypes: YAPf/f, Tek‐Cre; YAPf/w, Tek‐Cre; and YAPf/f. Retinal vascularization and astrocyte network were evaluated by whole‐mount fluorescence and Western blotting. In vitro, experiments were performed in an astrocyte and human microvascular endothelial cell (HMEC‐1) coculture model to analyse the mechanisms underlying the effect of endothelial YAP on astrocytes. Results In vivo, YAPf/f;Tek‐Cre mice showed delayed angiogenesis, sparse vessels and decreased glial fibrillary acidic protein (GFAP)+ astrocytes but aberrant growth of endothelial networks and immature astrocytes (platelet‐derived growth factor A, PDGFRA+ astrocytes) overgrowth. In vitro, Yap deletion attenuated the LIF release that delayed the maturation of retinal astrocyte which was consistent with the results of HMEC‐1—astrocyte coculture. The effect of YAP overexpression on LIF‐LIFR axis in HMEC‐1 interferes the GFAP expression of astrocyte. In contrast, LIF protein rescues the astrocytic GFAP expression when EC YAP was inhibited by siRNAs. Conclusions We show that EC yes‐associated protein (YAP) is not only a critical coactivator of Hippo signalling in retinal vessel development but also plays an essential role in retinal astrocyte maturation by regulating LIF production.

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YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development

Cited by 204 publications

References 58 publications

Distinct roles of VE ‐cadherin for development and maintenance of specific lymph vessel beds

Distinct roles of VE ‐cadherin for development and maintenance of specific lymph vessel beds

Gambogic acid impairs tumor angiogenesis by targeting YAP/STAT3 signaling axis

Retinal blood vessel‐origin yes‐associated protein (YAP) governs astrocytic maturation via leukaemia inhibitory factor (LIF)

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