Primary Cilia Are Not Required for Normal Canonical Wnt Signaling in the Mouse Embryo 英文参考文献.docVIP

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Primary Cilia Are Not Required for Normal Canonical Wnt Signaling in the Mouse Embryo 英文参考文献.doc

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Primary Cilia Are Not Required for Normal Canonical Wnt Signaling in the Mouse Embryo 英文参考文献

PrimaryCiliaAreNotRequiredforNormalCanonicalWnt SignalingintheMouseEmbryo PollonealJymmielR.Ocbina1,2,MiquelTuson1,KathrynV.Anderson1* 1DevelopmentalBiologyProgram,Sloan-KetteringInstitute,NewYork,NewYork,UnitedStatesofAmerica,2NeuroscienceProgram,WeillCornellGraduateSchoolof MedicalSciences,CornellUniversity,NewYork,NewYork,UnitedStatesofAmerica Abstract Background:Sonichedgehog(Shh)signalinginthemouserequiresthemicrotubule-basedorganelle,theprimarycilium. Theprimaryciliumisassembledandmaintainedthroughtheprocessofintraflagellartransport(IFT)andtheresponseto ShhisblockedinmousemutantsthatlackproteinsrequiredforIFT.AlthoughthephenotypesofmouseIFTmutantsdonot overlapwithphenotypesofknownWntpathwaymutants,recentstudiesreportdatasuggestingthattheprimarycilium modulatesresponsestoWntsignals. Methodology/Principal Findings: We therefore carried out a systematic analysis of canonical Wnt signaling in mutant embryosandcellsthatlackprimaryciliabecauseoflossoftheanterogradeIFTkinesin-IImotor(Kif3a)orIFTcomplexB proteins (Ift172 orIft88).We also analyzed mutantembryos withabnormal primaryciliadue todefectsin retrograde IFT (Dync2h1).ThemouseIFTmutantsexpressthecanonicalWnttargetAxin2andactivateatransgeniccanonicalWntreporter, BAT-gal, in the normal spatial pattern and to the same quantitative level as wild type littermates. Similarly, mouse embryonicfibroblasts(MEFs)derivedfromIFTmutantsrespondnormallytoaddedWnt3a.Theswitchfromcanonicalto non-canonical Wnt also appears normal in IFT mutant MEFs, as both wild-type and mutant cells do not activate the canonicalWntreporterinthepresenceofbothWnt3aandWnt5a. Conclusions: We conclude that loss of primary cilia or defects in retrograde IFT do not affect the response of the midgestationembryoorembryo-derivedfibroblaststoWntligands. Citation:OcbinaPJR,TusonM,AndersonKV(2009)PrimaryCiliaAreNotRequiredforNormalCanonicalWntSignalingintheMouseEmbryo.PLoSONE4(8): e6839.doi:10.1371/journal.pone.0006839 Editor:Carl-PhilippHeisenberg,MaxPla