Aberrant Otx2 Expression Enhances Migration and Induces Ectopic Proliferation of Hindbrain Neuronal Progenitor Cells 英文参考文献.docVIP

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Aberrant Otx2 Expression Enhances Migration and Induces Ectopic Proliferation of Hindbrain Neuronal Progenitor Cells 英文参考文献.doc

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Aberrant Otx2 Expression Enhances Migration and Induces Ectopic Proliferation of Hindbrain Neuronal Progenitor Cells 英文参考文献

AberrantOtx2ExpressionEnhancesMigrationand InducesEctopicProliferationofHindbrainNeuronal ProgenitorCells MatthewWortham,GenglinJin,JuliaLailaiSun,DarellD.Bigner,YipingHe,HaiYan* DepartmentofPathology,ThePediatricBrainTumorFoundationInstitute,andThePrestonRobertTischBrainTumorCenteratDuke,DukeUniversityMedicalCenter, Durham,NorthCarolina,UnitedStatesofAmerica Abstract Dysregulation of Otx2 is a hallmark of the pediatric brain tumor medulloblastoma, yet its functional significance in the establishment of these tumors is unknown. Here we have sought to determine the functional consequences of Otx2 overexpressioninthemousehindbraintocharacterizeitspotentialroleinmedulloblastomatumorigenesisandidentifythe celltypesresponsivetothislineage-specificoncogene.ExpressionofOtx2broadlyinthemousehindbrainresultedinthe accumulation of proliferative clusters of cells in the cerebellar white matter and dorsal brainstem of postnatal mice. We foundthatbrainstemectopiawerederivedfromneuronalprogenitorsoftherhombiclipandthatcerebellarectopiawere derived from granule neuron precursors (GNPs) that had migrated inwards from the external granule layer (EGL). These hyperplasiasexhibitedvariouscharacteristicsofmedulloblastomaprecursorcellsidentifiedinanimalmodelsofShhorWnt grouptumors,includingaberrantlocalizationandalteredspatiotemporalcontrolofproliferation.However,ectopiainduced by Otx2 differentiated and dispersed as the animals reached adulthood, indicating that factors restricting proliferative lifespanwerealimitingfactortofulltransformationofthesecells.ThesestudiesimplicatearoleforOtx2inalteringthe dynamicsofneuronalprogenitorcellproliferation. Citation:WorthamM,JinG,SunJL,BignerDD,HeY,etal.(2012)AberrantOtx2ExpressionEnhancesMigrationandInducesEctopicProliferationofHindbrain NeuronalProgenitorCells.PLoSONE7(4):e36211.doi:10.1371/journal.pone.0036211 Editor:JeffreyK.Harrison,UniversityofFlorida,UnitedStatesofAmerica ReceivedFebruary22,2012;AcceptedMarch28,2012;PublishedApril27,2012