Otx2 Is Involved in the Regional Specification of the Developing Retinal Pigment Epithelium by Preventing the Expression of Sox2 and Fgf8, Factors That Induce Neural Retina Differentiation 英文参考文献.docVIP

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Otx2 Is Involved in the Regional Specification of the Developing Retinal Pigment Epithelium by Preventing the Expression of Sox2 and Fgf8, Factors That Induce Neural Retina Differentiation 英文参考文献.doc

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Otx2IsInvolvedintheRegionalSpecificationofthe DevelopingRetinalPigmentEpitheliumbyPreventing theExpressionofSox2andFgf8,FactorsThatInduce NeuralRetinaDifferentiation DaisukeNishihara1,3,IchiroYajima2,HiromasaTabata3,MasatoNakai3,NagaharuTsukiji1, TatsuyaKatahira4,KazuhisaTakeda5,ShigekiShibahara5,HarukazuNakamura1,6,HiroakiYamamoto3* 1DepartmentofDevelopmentalBiologyandNeurosciences,GraduateSchoolofLifeSciences,TohokuUniversity,Sendai,Miyagi,Japan,2UnitofEnvironmentalHealth Sciences,DepartmentofBiomedicalSciences,CollegeofLifeandHealthSciences,ChubuUniversity,Kasugai,Aichi,Japan,3FacultyofBioscience,NagahamaInstituteof Bio-ScienceandTechnology,Nagahama,Shiga,Japan,4LaboratoryofDevelopmentalNeurobiology,GraduateSchoolofBrainScience,DoshishaUniversity,Kyotanabe, Kyoto, Japan, 5Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi, Japan, 6Department of Molecular Neurobiology,GraduateSchoolofLifeSciencesandInstituteofDevelopment,AgingandCancer,TohokuUniversity,Sendai,Miyagi,Japan Abstract Theretinalpigmentepithelium(RPE)sharesitsdevelopmentaloriginwiththeneuralretina(NR).WhenRPEdevelopmentis disrupted,cellsinthepresumptiveRPEregionabnormallydifferentiateintoNR-likecells.Therefore,thepreventionofNR differentiation in the presumptive RPE area seems to be essential for regionalizing the RPE during eye development. However, its molecular mechanisms are not fully understood. In this study, we conducted a functional inhibition of a transcriptionfactorOtx2,whichisrequiredforRPEdevelopment,usingearlychickembryos.Thefunctionalinhibitionof Otx2inchickeyes,usingarecombinantgeneencodingadominantnegativeformofOtx2,causedtheouterlayerofthe opticcup(theregionformingtheRPE,whenembryosnormallydevelop)toabnormallyformanectopicNR.Inthatectopic NR,thecharacteristicsoftheRPEdidnotappearandNRmarkerswereectopicallyexpressed.Intriguingly,therepressionof Otx2functionalsocausedtheectopicexpressionofFgf8andSox2intheouterlayeroftheopticcup(