A β-Catenin-Dependent Wnt Pathway Mediates Anteroposterior Axon Guidance in C. elegans Motor Neurons 英文参考文献.docVIP

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A β-Catenin-Dependent Wnt Pathway Mediates Anteroposterior Axon Guidance in C. elegans Motor Neurons 英文参考文献.doc

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A β-Catenin-Dependent Wnt Pathway Mediates Anteroposterior Axon Guidance in C. elegans Motor Neurons 英文参考文献

Ab-Catenin-DependentWntPathwayMediates AnteroposteriorAxonGuidanceinC.elegansMotor Neurons Ge′raldineS.Maro1*,MatthewP.Klassen2,KangShen1* 1HowardHughesMedicalInstitute,DepartmentofBiologyandPathology,StanfordUniversity,Stanford,California,UnitedStatesofAmerica,2NeurosciencesProgram, StanfordUniversity,Stanford,California,UnitedStatesofAmerica Abstract Background:Wntsaresecretedglycoproteinsthatregulatediverseaspectsofdevelopment,includingcellproliferation,cell fatespecificationanddifferentiation.Morerecently,Wntshavebeenshowntodirectaxonguidanceinvertebrates,fliesand worms.However,littleisknownabouttheintracellularsignalingpathwaysdownstreamofWntsinaxonguidance. Methodology/PrincipalFindings:HereweshowthattheposteriorC.elegansWntproteinLIN-44repelstheaxonsofthe adjacentD-typemotorneurons byactivatingitsreceptorLIN-17/Frizzled on theneurons. Moreover,mutationsin mig-5/ Disheveled,gsk-3,pry-1/Axin,bar-1/b-cateninandpop-1/TCF,alsocausedisruptedD-typeaxonpathfinding.ReducedBAR- 1/b-catenin activity in D-type axons leads to undergrowth of axons, while stabilization of BAR-1/b-catenin in a lin-23/ SCFb-TrCP mutantresultsinanoverextensionphenotype. Conclusions/Significance: Together, our data provide evidence that Wnt-mediated axon guidance can be transduced throughab-catenin-dependentpathway. Citation:MaroGS,KlassenMP,ShenK(2009)Ab-Catenin-DependentWntPathwayMediatesAnteroposteriorAxonGuidanceinC.elegansMotorNeurons.PLoS ONE4(3):e4690.doi:10.1371/journal.pone.0004690 Editor:AlainChe′dotal,InstitutdelaVision,France ReceivedNovember15,2008;AcceptedJanuary29,2009;PublishedMarch4,2009 Copyright: ? 2009 Maro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: Thisworkwas supported bytheW.M.KeckFoundation,the McKnightEndowmentFundandtheSearle ScholarAward.GSMisaHumanFrontier ScienceP