Antagonistic and Cooperative Actions of Kif7 and Sufu Define Graded Intracellular Gli Activities in Hedgehog Signaling 英文参考文献.docVIP

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Antagonistic and Cooperative Actions of Kif7 and Sufu Define Graded Intracellular Gli Activities in Hedgehog Signaling 英文参考文献.doc

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Antagonistic and Cooperative Actions of Kif7 and Sufu Define Graded Intracellular Gli Activities in Hedgehog Signaling 英文参考文献

AntagonisticandCooperativeActionsofKif7andSufu DefineGradedIntracellularGliActivitiesinHedgehog Signaling KelvinKingLoLaw1,2,ShigeruMakino3,RongMo1,XiaoyunZhang1,VijithaPuviindran1 ,Chi- chungHui1,2 * 1PrograminDevelopmentalStemCellBiology,TheHospitalforSickChildren,TorontoMedicalDiscoveryTower,Toronto,Ontario,Canada,2DepartmentofMolecular Genetics,UniversityofToronto,Toronto,Ontario,Canada,3MutagenesisandGenomicsTeam,RIKENBioResourceCenter,Koyadai,Tsukuba,Ibaraki,Japan Abstract Graded Hedgehog (Hh) signaling governs the balance of Gli transcriptional activators and repressors to specify diverse ventral cell fates in the spinal cord. It remains unclear how distinct intracellular Gli activity is generated. Here, we demonstrate that Sufu acts universally as a negative regulator of Hh signaling, whereas Kif7 inhibits Gli activity in cooperation with, and independent of, Sufu. Together, they deter na?¨ve precursors from acquiring increasingly ventral identity.WeshowthatKif7isalsorequiredtoestablishhighintracellularGliactivitybyantagonizingtheSufu-inhibitionof Gli2.Strikingly,byabolishingthenegativeregulatoryactionofSufu,diverseventralcellfatescanbespecifiedintheabsence ofextracellularHhsignaling.ThesedatasuggestthatSufuistheprimaryregulatorofgradedHhsignalingandestablishthat theantagonisticandcooperativeactionsofKif7andSufuareresponsibleforsettingupdistinctGliactivityinventralcell fatespecification. Citation:LawKKL,MakinoS,MoR,ZhangX,PuviindranV,etal.(2012)AntagonisticandCooperativeActionsofKif7andSufuDefineGradedIntracellularGli ActivitiesinHedgehogSignaling.PLoSONE7(11):e50193.doi:10.1371/journal.pone.0050193 Editor:BenHogan,UniversityofQueensland,Australia ReceivedSeptember7,2012;AcceptedOctober22,2012;PublishedNovember16,2012 Copyright:?2012Lawetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:Thiswo