Dkk1 Regulates Ventral Midbrain Dopaminergic Differentiation and Morphogenesis 英文参考文献.docVIP

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Dkk1 Regulates Ventral Midbrain Dopaminergic Differentiation and Morphogenesis 英文参考文献.doc

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Dkk1 Regulates Ventral Midbrain Dopaminergic Differentiation and Morphogenesis 英文参考文献

Dkk1RegulatesVentralMidbrainDopaminergic DifferentiationandMorphogenesis DiogoRibeiro1,KristinaEllwanger2.,De′sire′eGlagow3.,SpyridonTheofilopoulos1,NinaS.Corsini3¤, AnaMartin-Villalba3,ChristofNiehrs2,ErnestArenas1* 1SectionofMolecularNeurobiology,DepartmentofMedicalBiochemistryandBiophysics,KarolinskaInstitute,Stockholm,Sweden,2DivisionofMolecularEmbryology, DKFZ-ZMBHAlliance,GermanCancerResearchCenter,Heidelberg,Germany,3DivisionofMolecularNeurobiology,GermanCancerResearchCenter,Heidelberg,Germany Abstract Dickkopf1(Dkk1)isaWnt/b-catenininhibitorthatparticipatesinmanyprocessesduringembryonicdevelopment.Oneofits rolesduringembryogenesisistoinduceheadformation,sinceDkk1-nullmicelackheadstructuresanteriortomidbrain.The Wnt/b-catenin pathway is also known to regulate different aspects of ventral midbrain (VM) dopaminergic (DA) neuron development and, in vitro, Dkk1-mediated inhibition of the Wnt/b-catenin pathway improves the DA differentiation in mouseembryonicstemcells(mESC).However,theinvivofunctionofDkk1onthedevelopmentofmidbrainDAneurons remainstobeelucidated.HereweexaminedDkk1+/2embryosandfoundthatDkk1isrequiredforthedifferentiationofDA precursors/neuroblasts into DA neurons at E13.5. This deficit persisted until E17.5, when a defect in the number and distributionofVMDAneuronswasdetected.Furthermore,analysisofthefewDkk12/2embryosthatsurviveduntilE17.5 revealed a more severe loss of midbrain DA neurons and morphogenesis defects. Our results thus show that Dkk1 is requiredformidbrainDAdifferentiationandmorphogenesis. Citation: Ribeiro D, Ellwanger K, Glagow D, Theofilopoulos S, Corsini NS, et al. (2011) Dkk1 Regulates Ventral Midbrain Dopaminergic Differentiation and Morphogenesis.PLoSONE6(2):e15786.doi:10.1371/journal.pone.0015786 Editor:MikeKarl,CenterforRegenerativeTherapiesDresden,Germany ReceivedJuly28,2010;AcceptedNovember24,2010;PublishedFebruary11,2011 Copyright: ? 2011 Ribeiro et al. This is an open-access article distributed under the terms of the Cre