Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development 英文参考文献.docVIP

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Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development 英文参考文献.doc

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Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development 英文参考文献

EffectofVascularCadherinKnockdownonZebrafish VasculatureduringDevelopment IanC.Mitchell1,TimothyS.Brown1,LanceS.Terada2,JamesF.Amatruda3*,FiemuE.Nwariaku1* 1DivisionofGastrointestinalandEndocrineSurgery,DepartmentofSurgery,UniversityofTexasSouthwesternMedicalCenter,Dallas,Texas,UnitedStatesofAmerica, 2Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America, 3Departments of Pediatrics, Molecular BiologyandInternalMedicine,UniversityofTexasSouthwesternMedicalCenter,Dallas,Texas,UnitedStatesofAmerica Abstract Background: Vascular endothelial cadherin (VE-cad) is essential for endothelial barrier integrity and vascular sprouting. However,theroleofthisimportantproteinincardiovasculardevelopmentisonlyrecentlybecomingapparent. Methodology/Principal Findings: To characterize the role of VE-cadherin in cardiovascular development, we analyzed cardiovascular development in a zebrafish VE-cad knockdown model. Embryos deficient in VE-cad show profoundly impaired cardiac development despite having apparently normal peripheral vasculature. Initial formation of the heart proceeds normally in knockdown embryos, but subsequent looping morphogenesis is impaired. Consistent with these results, VE-cad knockdown embryos demonstrate impaired cardiac function and early circulatory arrest. Histologic examinationofknockdownembryosshowspersistent,abnormalseparationoftheendocardialandmyocardiallayers.Using transmissionelectronmicroscopy,wedemonstratethatendocardialjunctionsformpoorlyinVE-cadknockdownembryos, withresultingleakacrosstheendotheliallayerandreductioninthedensityofthecardiacjelly. Conclusions:OurresultsdemonstrateasignificantroleforVE-cadherinincardiacdevelopmentindependentofitseffects ontheformationoftheperipheralvasculature. Citation: Mitchell IC, Brown TS, Terada LS, Amatruda JF, Nwariaku FE (2010) Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development.PLoSONE5(1):e8807.doi:10.1371/jour