Foxp2 Regulates Gene Networks Implicated in Neurite Outgrowth in the Developing Brain 英文参考文献.docVIP

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Foxp2 Regulates Gene Networks Implicated in Neurite Outgrowth in the Developing Brain 英文参考文献.doc

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Foxp2 Regulates Gene Networks Implicated in Neurite Outgrowth in the Developing Brain 英文参考文献

Foxp2RegulatesGeneNetworksImplicatedinNeurite OutgrowthintheDevelopingBrain SonjaC.Vernes1¤a,PeterL.Oliver2,ElizabethSpiteri3¤b,HelenE.Lockstone1,RathiPuliyadi1,JenniferM. Taylor1,JosesHo1,CedricMombereau4,ArielBrewer4,ErnestoLowy1,Je′ro?meNicod1 ,Matthias Groszer1,4,DilairBaban1,NatashaSahgal1,Jean-BaptisteCazier1,JiannisRagoussis1,KayE.Davies2, DanielH.Geschwind3,5,SimonE.Fisher1,6 * 1WellcomeTrustCentreforHumanGenetics,UniversityofOxford,Oxford,UnitedKingdom,2MedicalResearchCouncilFunctionalGeneticsUnit,UniversityofOxford, Oxford,UnitedKingdom,3PrograminNeurogenetics,DepartmentofNeurology,UniversityofCaliforniaLosAngeles,LosAngeles,California,UnitedStatesofAmerica, 4INSERMInstituteduFera`Moulin,UniversityPierreandMarieCurie,UMR-S839,Paris,France,5SemelInstituteandDepartmentofHumanGenetics,DavidGeffenSchool of Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 6Language and Genetics Department, Max Planck Institute for Psycholinguistics,Nijmegen,TheNetherlands Abstract Forkhead-boxproteinP2isatranscriptionfactorthathasbeenassociatedwithintriguingaspectsofcognitivefunctionin humans, non-human mammals, and song-learning birds. Heterozygous mutations of the human FOXP2 gene cause a monogenic speech and language disorder. Reduced functional dosage of the mouse version (Foxp2) causes deficient cortico-striatal synaptic plasticity and impairs motor-skill learning. Moreover, the songbird orthologue appears critically importantforvocallearning.Acrossdiversevertebratespecies,thiswell-conservedtranscriptionfactorishighlyexpressedin thedevelopingandadultcentralnervoussystem.VerylittleisknownaboutthemechanismsregulatedbyFoxp2during brain development. We used anintegrated functional genomics strategy to robustly define Foxp2-dependent pathways, bothdirectandindirecttargets,intheembryonicbrain.Specifically,weperformedgenome-wideinvivoChIP–chipscreens for Foxp2-binding and thereby identified a set of 264 high-confidence neural ta