Activated MAPK/ERK Kinase (MEK-1) Induces Transdifferentiation of Pigmented Epithelium into Neural Retina
[摘要] Duringvertebrateeyedevelopment,theopticvesicleoriginatingfromtheneuroectodermispartitionedintoadomainthatwillgiverisetotheneuralretina(NR)andanotherthatwillgiverisetotheretinalpigmentedepithelium(RPE).PreviousstudieshaveshownthatectopicexpressionofFGFsintheRPEinducesRPE-to-NRtransdifferentiation.Similarly,anaturallyoccurringmutationofthetranscriptionfactorMitfinmouseresultedintheformationofasecondneuralretinainplaceofthedorsalRPE,buttheputativesignalingpathwaylinkingFGFtoMitfregulationispresentlyunknown.Inculturesofneuralcrest-derivedmelanocytes,theMAPKpathwaywasrecentlyshowntotargettheMitftranscriptionfactorforubiquitin-dependentproteolysis,resultinginarapiddegradationanddownregulation.Inthepresentstudy,weshowthatectopicexpressionofaconstitutivelyactivatedalleleofMEK-1,theimmediateupstreamactivatoroftheMAPKERK,inchickenembryonicretinainovo,inducestransdifferentiationoftheRPEintoaneural-likeepitheliumthatiscorrelatedwithadownregulationofMitfexpressioninthepresumptiveRPE.
[发布日期] [发布机构]
[效力级别] [学科分类] 生物科学（综合）
[关键词] retina;MAPK;Ras;Raf;pigment;microphthalmia;FGF;signaling;embryo [时效性]
