Control of Skeletal Patterning by EphrinB1-EphB Interactions

Compagni, Amelia; Logan, Malcolm; Klein, Rüdiger; Adams, Ralf H.

doi:10.1016/s1534-5807(03)00198-9

Cited by 213 publications

(212 citation statements)

References 25 publications

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“…Alternatively, LacZ-specific antibody (MP Cappel #59761, 1:400) was used for multicolorimmunofluorescence staining, as described previously 56 Following isolectin-B4 staining, retinas were stained with BrdU-specific antibody (1:100, BD).…”

Section: Methodsmentioning

confidence: 99%

Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function

Yoshioka

Yoshida

Chen

et al. 2012

Nat Med

176

259

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Class II α-isoform of phosphatidylinositol 3-kinases (PI3K-C2α) is localized in endosomes, the trans-Golgi network and clathrin-coated vesicles, however, its functional role is little understood. Global or endothelial cell (EC)-specific targeted disruption of PI3K-C2α resulted in embryonic lethality due to defects in sprouting angiogenesis and vascular maturation. PI3K-C2α knockdown in ECs induced decreased phospatidylinositol 3-phosphate-enriched endosomes, impaired endosomal trafficking, and defective delivery of VE-cadherin to EC junctions and its assembly. PI3K-C2α knockdown also impeded cell signaling including vascular endothelial growth factor receptor internalization and endosomal RhoA activation. These together led to defective EC migration, proliferation, tube formation and barrier integrity. Endothelial PI3K-C2α deletion suppressed post-ischemic and tumor angiogenesis, and diminished vascular barrier function, with greatly augmented susceptibility to anaphylaxis and a higher incidence of dissecting aortic aneurysm formation in response to angiotensin II infusion. Thus, PI3K-C2α plays a crucial role in vascular formation and barrier integrity, and represents a new therapeutic target for vascular diseases. 3Formation of the vascular network by vasculogenesis and angiogenesis is essential for embryonic development, repair and remodeling of tissues in adults, as well as tumor growth. The angiogenic response to vascular endothelial growth factor (VEGF) and other factors begins with vascular leakage and dissolution of the subendothelial basement membrane, followed by proliferation and migration of vascular EC 1,2 . Then, formation of the intercellular junctions results in initial sprouts from existing vessels. The newly formed endothelial tubes are associated with mural cells, i.e. smooth muscle cells (SMC) and pericytes, thus becoming mature and stabilized 3 . Tightness of the intercellular junctions, particularly adherens junctions composed of VE-cadherin, controls vascular permeability 4,5 . Quiescent, stabilized vasculature with intact barrier integrity dominates in the healthy condition. In contrast, in pathological conditions, such as tumors, the vasculature is generally inmaturate and leaky. In the case of vascular insult such as excessive angiotensin II (Ang II) activity, increased vascular permeability is asssociated with leukocyte infiltration in the vascular wall and vascular disruption 6,7 . Therefore, stabilization of the vasculature and maintenance of vascular integrity is essential for vascular and tissue homeostasis 8,9 .PI3Ks are an enzyme family that phosphorylates membrane inositol lipids at the 3' position of the inositol ring. The lipid products of PI3Ks serve as important intracellular messengers by interacting with effector proteins, which include protein kinases, guanine nucleotide exchangers for G proteins, and actin cytoskeleton-regulating proteins. Through these actions, PI3Ks regulate a diverse array of cellular processes 10-12 .PI3Ks comprise three classes. Class I PI...

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Section: Methodsmentioning

confidence: 99%

Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function

Yoshioka

Yoshida

Chen

et al. 2012

Nat Med

176

259

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“…Conditional Gene KO Mice-Efnb1 null mutation causes embryonic lethality (25). To study the function of Efnb1 in VMSCs, we generated conditional KO mice (18).…”

Section: Generation Of Smc-specific Efnb1mentioning

confidence: 99%

Possible Role of Efnb1 Protein, a Ligand of Eph Receptor Tyrosine Kinases, in Modulating Blood Pressure

Luo

Thorin

et al. 2012

Journal of Biological Chemistry

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Background: Currently, there is no knowledge about the function of ephrins in vascular smooth muscle contraction and blood pressure regulation. Results: Stimulating Efnb1 reduces vascular smooth muscle cell contraction. Efnb1 null mutation increases RhoA activation and heightens blood pressure in mice. Conclusion: Efnb1 can regulate vessel tone and blood pressure. Significance: We identified a new group of molecules capable of regulating blood pressure.

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“…Cells were maintained in 5% RPMI 1640 medium supplemented with 100 units/ml mrIL-2, 10 g/ml brefeldin A, 10 M gp (33)(34)(35)(36)(37)(38)(39)(40)(41) or gp(61-80) peptide. After 5 h of incubation at 37°C, cells were stained with phycoerythrin-conjugated rat anti-mouse CD8␣ or CD4 mAbs and 7-aminoactinomycin D. Cells were then fixed, permeabilized and stained with allophycocyanin-rat anti-mouse TNF-␣ and FITC-rat anti-mouse IFN-␥ mAbs.…”

Section: Generation Of T Cell-specific Efnb1 and Efnb2mentioning

confidence: 99%

Efnb1 and Efnb2 Proteins Regulate Thymocyte Development, Peripheral T Cell Differentiation, and Antiviral Immune Responses and Are Essential for Interleukin-6 (IL-6) Signaling

Luo

Charpentier

Wang

et al. 2011

Journal of Biological Chemistry

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Background: Ephrins (Efn) are the ligands of Eph kinases. The roles of Efn in the T cell compartment are studied. Results: Efnb1 and Efnb2 double knock-out mice showed compromised thymocyte development, Th1 and Th17 function, IL-6 receptor signaling, and antivirus responses. Conclusion: Efnb1 and Efnb2 are involved in the T cell development and function. Significance: This study has revealed novel biological roles of Efns.

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Control of Skeletal Patterning by EphrinB1-EphB Interactions

Cited by 213 publications

References 25 publications

Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function

Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function

Possible Role of Efnb1 Protein, a Ligand of Eph Receptor Tyrosine Kinases, in Modulating Blood Pressure

Efnb1 and Efnb2 Proteins Regulate Thymocyte Development, Peripheral T Cell Differentiation, and Antiviral Immune Responses and Are Essential for Interleukin-6 (IL-6) Signaling

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