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, Claudio; Potente, Michael; Gerhardt, Holger

doi:10.1101/174185

Cited by 49 publications

(76 citation statements)

References 54 publications

(60 reference statements)

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“…Lipid phosphate phosphatase 3 (LPP3) is an ectoenzyme expressed on the surface of ECs and seems to contribute predominantly to the degradation of LPA in blood (63). Yukiura et al reported that LPP3 is expressed locally in HUVECs, i.e., LPP3 is localized results in HUVECs (36), it is noteworthy that the Notch inhibitor DAPT restored the sprouting defects of YAP/TAZ siRNA-treated HUVECs in our study. YAP/TAZ-mediated DLL4 suppression is likely to be involved in LPA4/LPA6-mediated sprouting angiogenesis, as DAPT again restored sprouting defects in LPA4/LPA6 siRNA-treated HUVECs.…”

Section: Discussionsupporting

confidence: 67%

“…YAP nuclear localization was impaired in the angiogenic front of Lpa4;Lpa6 iΔEC retinas. Several independent studies have revealed that endothelial YAP/TAZ mediate sprouting angiogenesis (31)(32)(33)(34)(35)(36). In this context, we propose LPA4 and LPA6 as regulators of sprouting angiogenesis that repress DLL4 expression by activating YAP/TAZ in ECs.…”

Section: Discussionmentioning

confidence: 64%

“…Indeed, Barry et al previously showed that transgenic overexpression of a phospho-deficient YAP mutant, which exhibits enhanced nuclear localization, repressed Dll4 gene expression in mouse intestinal epithelium (60). The involvement of nuclear YAP/TAZ in LPA4/LPA6-induced angiogenesis could provide a possible reason for the apparently milder phenotypes of Lpa4; Lpa6 iΔEC retinas compared with those observed in Yap;Taz iΔEC retinas (31)(32)(33)36), as cytoplasmic YAP/TAZ also exert angiogenic functions in ECs. In particular, YAP/TAZ regulate CDC42 in the migration of tip ECs (33).…”

Section: Discussionmentioning

confidence: 99%

“…A previous report showed that LPA-induced Gα12/Gα13 signaling activated YAP in HEK293 cells (30). Recently, several independent studies revealed that endothelial YAP/TAZ mediate sprouting angiogenesis (31)(32)(33)(34)(35)(36). However, the biological significance of GPCR-induced YAP/TAZ activation is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Lysophosphatidic acid–induced YAP/TAZ activation promotes developmental angiogenesis by repressing Notch ligand Dll4

Yasuda

Kobayashi

Akahoshi

et al. 2019

Journal of Clinical Investigation

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al cooperation between LPA4 and LPA6 is essential for embryonic development. Since Lpa4;Lpa5-DKO and Lpa5;Lpa6-DKO mice were born at the expected Mendelian ratios and had no obvious abnormalities (Supplemental Tables 4 and 5), LPA5 is unlikely to be involved in embryonic development. To examine the roles of LPA4 and LPA6 in embryonic development, yolk sac and embryo proper were observed at various stages of gestation. At E8.5, both Lpa4;Lpa6-DKO yolk sac and embryo proper appeared normal (Supplemental Figure 1, A and B). However, at E9.5-10.5, almost all of Lpa4;Lpa6-DKO embryos proper had various morphological abnormalities, such as severe pericardial effusion (Figure 1A and Supplemental Figure 1, B-D), axial turning abnormality (Supplemental Figure 1, B, E, and F), and developmental delay (Figure 1, A and B, and Supplemental Figure 1, B, G, and H). DKO yolk sacs lacked large blood vessels at E9.5-10.5, whereas WT yolk sacs had well-developed blood vessels (Figure 1B and Supplemental Figure 1, A, I, and J). We observed that all DKO embryos died by E11.5 (Supplemental Figure 1, B, K, and L, and Supplemental Table 6). Histological analysis showed that the endoderm and mesoderm of the yolk sacs were more widely separated in the DKO tissue (Figure 1C). Despite this vascular defect, erythrocytes were present in Lpa4;Lpa6-DKO yolk sacs (Figure 1C). Blood vessel-stained whole-mount embryos at E10.5 revealed that DKO embryos had enlarged dorsal aortae and poor vascular networks in the head and intersomitic regions, compared with WT embryos (Figure 1D). Furthermore, blood vessel-stained cross sections of embryos at E9.5 also revealed that DKO embryos had enlarged dorsal aortae and thinned neural tubes, compared with WT embryos (Figure 1E). These results strongly suggest that both LPA4 and LPA6 are indispensable for embryonic angiogenesis. Endothelial LPA4 and LPA6 are involved in retinal angiogenesis. Previously, we detected mRNA expression of Lpa4 and LPA6 in vascular ECs (8, 16). To investigate the functional roles of endothelial LPA4 and LPA6, we generated a tamoxifen-inducible and EC-specific Lpa4/Lpa6 deletion mouse line by crossing Lpa4;Lpa6 double-floxed mutants with transgenic mice carrying Cdh5-CreER T2 (ref. 37, Figure 2A, and Supplemental Figure 2A). The resulting Lpa4 fl/fl(Y) Lpa6 fl/fl Cdh5-CreER T2 mice (termed hereafter Lpa4; Lpa6 iΔEC) were treated with tamoxifen from P1 to P3. Allele-specific PCR confirmed recombination of both floxed alleles in the tails of Lpa4;Lpa6 iΔEC mice at P5 (Supplemental Figure 2B). At P5, we found that the radial expansion, EC area, and retinal blood vessel branching were significantly reduced in Lpa4;Lpa6 iΔEC mice compared with those in control CreER T2-negative Lpa4 fl/fl(Y) ;Lpa6 fl/fl littermates (Figure 2, C and F-H). At the angiogenic front, sprouts of retinal vessels were significantly reduced in Lpa4;Lpa6 iΔEC retina (Figure 2, D and I). Additionally, both the number and length of sprouting filopodia were significantly reduced in Lpa4;Lpa6 iΔEC retina (Figure 2, E, J...

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lysophosphatidic acid–induced YAP/TAZ activation promotes developmental angiogenesis by repressing Notch ligand Dll4

Yasuda

Kobayashi

Akahoshi

et al. 2019

Journal of Clinical Investigation

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“…The nuclear localization and thus the strength of YAP/TAZ signaling depends on ECM rigidity and actin stress fiber formation (Dupont et al, 2011). Recent experiments revealed that the ECM stiffness-dependent regulation of YAP/TAZ localization is also sensitive to the density and spacing of integrin receptors (Oria et al, 2017), while an independent study identified a role of YAP/TAZ in regulating the stability of AJs through modulation of BMP signaling (Neto et al, 2018). It has been also speculated that nuclear entry of YAP is modulated by force-dependent regulation of nuclear pores (Elosegui-Artola et al, 2017).…”

Section: Crosstalk Through Common Adaptor Proteins and Mechano-chemicmentioning

confidence: 99%

Unforgettable force – crosstalk and memory of mechanosensitive structures

Kanoldt

Fischer

Grashoff

2018

Biological Chemistry

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The ability of cells to sense and respond to mechanical stimuli is crucial for many developmental and homeostatic processes, while mechanical dysfunction of cells has been associated with numerous pathologies including muscular dystrophies, cardiovascular defects and epithelial disorders. Yet, how cells detect and process mechanical information is still largely unclear. In this review, we outline major mechanisms underlying cellular mechanotransduction and we summarize the current understanding of how cells integrate information from distinct mechanosensitive structures to mediate complex mechanoresponses. We also discuss the concept of mechanical memory and describe how cells store information on previous mechanical events for different periods of time.

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A new strategy for the decellularization of whole organs by hydrostatic pressure

Morales‐Guerrero

Varela‐Echavarría

Flores

et al. 2022

Biotechnology Progress

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Tissue engineering has been able to develop novel decellularization-recellularization techniques, which facilitates the research for the generation of functional organs. This is based in the initial obtention of the organ's extracellular matrix (ECM). Therefore, any improvement in the decellularization process would have a positive impact in the results of the recellularization process. Nevertheless, commonly the methods and equipment employed for this process are expensive and thus limit the access of this technique to various research groups globally. To develop a decellularization technique with the exclusive use of hydrostatic pressure of detergent solutions, to have an easily accessible and low-cost technique that meets the basic requirements of acellularity and functionality of the ECM. This experimental study was performed in 10 male Wistar rats, obtaining the liver to carry out serial washes, with 1%, 2%, and 3% Triton X-100 solutions and 0.1% SDS. The washes were performed by using a gravity perfusion system (GPS), which assured us a continuous hydrostatic pressure of 7.5 mmHg. The obtained ECM was processed using stains and immunostaining to determine the residual cell content and preservation of its components. The staining showed a removal of cellular and nuclear components of approximately 97% of the acellular ECM, with an adequate three-dimensional pattern of collagen and proteoglycans. Furthermore, the acellular ECM allowed the viability of a primary hepatocyte culture. The use of the GPS decellularization technique allowed us to obtain an acellular and functional ECM, drastically reducing experimentation costs.

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

Abstract: 51signaling to balance endothelial cell distribution in angiogenic vessels.

Cited by 49 publications

References 54 publications

Lysophosphatidic acid–induced YAP/TAZ activation promotes developmental angiogenesis by repressing Notch ligand Dll4

Lysophosphatidic acid–induced YAP/TAZ activation promotes developmental angiogenesis by repressing Notch ligand Dll4

Unforgettable force – crosstalk and memory of mechanosensitive structures

A new strategy for the decellularization of whole organs by hydrostatic pressure

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