prox1b Activity Is Essential in Zebrafish Lymphangiogenesis 英文参考文献.docVIP

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prox1b Activity Is Essential in Zebrafish Lymphangiogenesis 英文参考文献.doc

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prox1b Activity Is Essential in Zebrafish Lymphangiogenesis 英文参考文献

prox1bActivityIsEssentialinZebrafish Lymphangiogenesis LucaDelGiacco1*,AnnaPistocchi2,AnnaGhilardi1 1DepartmentofBiology,Universita` degliStudidiMilano,Milan,Italy,2DivisionofRegenerativeMedicine,SanRaffaeleScientificInstitute,Milan,Italy Abstract Background: The lymphatic vascular system, draining interstitial fluids from most tissues and organs, exerts crucial functionsinseveralphysiologicalandpathologicalprocesses.LymphaticsystemdevelopmentdependsonProx1,thefirst markertobeexpressedintheendothelialcellsofthecardinalveinfromwherelymphvesselsoriginate.Prox1orthologin the optically clear, easily manipulated zebrafish model has been previously isolated and its contribution to lymphangiogenesis has been clarified. Because of a round of genome duplication occurred at the base of teleosts radiation,severalzebrafishgeneshavebeenretainedinduplicatethroughevolution.Weinvestigatedforthepresenceof additionalprox1genesanddeterminedtheirroleinzebrafishlymphangiogenesis. Methodology/Principal Findings: We isolated a second ortholog, named prox1b, and analyzed its expression during developmentbywholemountinsituhybridization(WISH).Wedetectedstrongprox1bexpressionintheendotheliumofthe posterior cardinal vein (PCV) from where lymphatic precursors originate. To analyze prox1b involvement in lymphangiogenesis weutilized thefli1:GFP transgenics andfollowed theformation of thetoracic duct (TD), theprimary lymphvesselinfish,afterprox1bknockdown.Ourfindingsclearlydemonstratedthattheabsenceofprox1bactivityseverely hamperstheformationoftheTD. Conclusions/Significance:Thisworkprovidessubstantialprogresstowardtheunderstandingofzebrafishlymphangiogen- esis.Inlightofthefeaturessharedbythelymphaticsystemsofzebrafishandhighervertebrates,theestablishmentofsuch lymphaticmodelwillprovideapowerfultooltostudy,forinstance,disordersofbodyfluidhomeostasis,inflammationand cancermetastasis,andmayultimatelycontributetonoveltherapies. Citation: Del Giacco L, Pistocchi A, Ghilardi A (2010) prox1b