Endothelial Expression of TGFβ Type II Receptor Is Required to Maintain Vascular Integrity during Postnatal Development of the Central Nervous System 英文参考文献.docVIP

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Endothelial Expression of TGFβ Type II Receptor Is Required to Maintain Vascular Integrity during Postnatal Development of the Central Nervous System 英文参考文献.doc

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Endothelial Expression of TGFβ Type II Receptor Is Required to Maintain Vascular Integrity during Postnatal Development of the Central Nervous System 英文参考文献

EndothelialExpressionofTGFbTypeIIReceptorIs RequiredtoMaintainVascularIntegrityduringPostnatal DevelopmentoftheCentralNervousSystem KathleenR.Allinson1,HyeShinLee2,MarcusFruttiger3,JosephMcCarty2,HelenM.Arthur1* 1InstituteofGeneticMedicine,NewcastleUniversity,NewcastleuponTyne,UnitedKingdom,2UniversityofTexasMDAndersonCancerCenter,Houston,Texas,United StatesofAmerica,3UCLInstituteofOphthalmology,UniversityCollege,London,UnitedKingdom Abstract TGFbsignallinginendothelialcellsisimportantforangiogenesisinearlyembryonicdevelopment,butlittleisknownabout itsroleinearlypostnatallife.ToaddressthisweusedatamoxifeninducibleCre-LoxPstrategyinneonatalmicetodeplete the TypeII TGFb receptor (Tgfbr2) specifically in endothelial cells. This resulted in multiple micro-haemorrhages, and glomeruloid-likevasculartuftsthroughoutthecerebralcorticesandhypothalamusofthebrainaswellasinretinaltissues.A detailedexaminationoftheretinaldefectsinthesemutantsrevealedthatendothelialadherensandtightjunctionswerein place, pericytes wererecruited andthere wasno failure of vascularsmoothmuscle differentiation. However, thedeeper retinalplexusfailedtoforminthesemutantsandtheangiogenicsproutsstalledintheirprogresstowardstheinnernuclear layer. Instead the leading endothelial cells formed glomerular tufts with associated smooth muscle cells. This evidence suggests that TGFb signalling is not required for vessel maturation, but is essential for the organised migration of endothelial cells as they begin to enter the deeper layers of the retina. Thus, TGFb signalling is essential in vascular endothelialcellsformaintainingvascularintegrityattheangiogenicfrontasitmigratesintodevelopingneuraltissuesin earlypostnatallife. Citation:AllinsonKR,LeeHS,FruttigerM,McCartyJ,ArthurHM(2012)EndothelialExpressionofTGFbTypeIIReceptorIsRequiredtoMaintainVascularIntegrity duringPostnatalDevelopmentoftheCentralNervousSystem.PLoSONE7(6):e39336.doi:10.1371/journal.pone.0039336 Editor:JingChen,Children’sHospitalBoston,UnitedSta