Attenuation of Notch and Hedgehog Signaling Is Required for Fate Specification in the Spinal Cord 英文参考文献.docVIP

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Attenuation of Notch and Hedgehog Signaling Is Required for Fate Specification in the Spinal Cord 英文参考文献.doc

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Attenuation of Notch and Hedgehog Signaling Is Required for Fate Specification in the Spinal Cord 英文参考文献

AttenuationofNotchandHedgehogSignalingIs RequiredforFateSpecificationintheSpinalCord PengHuang1*,FengzhuXiong2,SeanG.Megason2,AlexanderF.Schier1* 1Department ofMolecularandCellular Biology, Center forBrain Science,HarvardStem CellInstitute, BroadInstitute,Centerfor Systems Biology, Harvard University, Cambridge,Massachusetts,UnitedStatesofAmerica,2DepartmentofSystemsBiology,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica Abstract During the development of the spinal cord, proliferative neural progenitors differentiate into postmitotic neurons with distinctfates.Howcellsswitchfromprogenitorstatestodifferentiatedfatesispoorlyunderstood.Toaddressthisquestion, westudiedthedifferentiationofprogenitorsinthezebrafishspinalcord,focusingonthedifferentiationofKolmer-Agduhr0 (KA0)interneuronsfromlateralfloorplate(LFP)progenitors.InvivocelltrackingdemonstratesthatKA0cellsaregenerated from LFP progenitors by both symmetric and asymmetric cell divisions. A photoconvertible reporter of signaling history (PHRESH)revealsdistincttemporalprofilesofHhresponse:LFPprogenitorscontinuouslyrespondtoHh,whileKA0cellslose Hhresponseupondifferentiation.HhsignalingisrequiredinLFPprogenitorsforKA0fatespecification,butprolongedHh signalinginterfereswithKA0differentiation.NotchsignalingactspermissivelytomaintainLFPprogenitorcells:activationof Notchsignalingpreventsdifferentiation,whereasinhibitionofNotchsignalingresultsindifferentiationofectopicKA0cells. TheseresultsindicatethatneuralprogenitorsdependonNotchsignalingtomaintainHhresponsivenessandrelyonHh signaling to induce fate identity, whereas proper differentiation depends on the attenuation of both Notch and Hh signaling. Citation: Huang P, Xiong F, Megason SG, Schier AF (2012) Attenuation of Notch and Hedgehog Signaling Is Required for Fate Specification in the Spinal Cord.PLoSGenet8(6):e1002762.doi:10.1371/journal.pgen.1002762 Editor:MaryC.Mullins,UniversityofPennsylvaniaSchoolofMedicine,UnitedStatesofAmerica ReceivedDece