Ewing Sarcoma Protein Ewsr1 Maintains Mitotic Integrity and Proneural Cell Survival in the Zebrafish Embryo 英文参考文献.docVIP

EwingSarcomaProteinEwsr1MaintainsMitoticIntegrity andProneuralCellSurvivalintheZebrafishEmbryo MizukiAzuma*,LisaJ.Embree,HatemSabaawy,DennisD.Hickstein ExperimentalTransplantationandImmunologyBranch,CenterforCancerResearch,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda, Maryland,UnitedStatesofAmerica Background. TheEwingsarcomabreakpoint region1gene (EWSR1),alsoknownasEWS,isfused toa numberofdifferent partner genes as a result of chromosomal translocation in diverse sarcomas. Despite the involvement of EWSR1 in these diversesarcomas,theinvivofunctionofwildtypeEWSR1remainsunclear.PrincipalFindings.Weidentifiedtwozebrafish EWSR1 orthologues, ewsr1a and ewsr1b, and demonstrate that both genes are expressed maternally, and are expressed ubiquitouslythroughoutzebrafishembryonicdevelopment.Morpholinoinducedknockdownofbothzebrafish ewsr1genes led to mitotic defects with multipolar or otherwise abnormal mitotic spindles starting from the bud stage (10hour post- fertilization(hpf)).Theabnormalitiesinmitoticspindleswerefollowedbyp53-mediatedapoptosisinthedevelopingcentral nervous system (CNS) leading to a reduction in the number of proneural cells, disorganization of neuronal networks, and embryoniclethalityby5dayspost-fertilization.siRNAsilencingofEWSR1inHelacellsresultedinmitoticdefectsaccompanied byapoptoticcelldeath,indicatingthattheroleofEWSR1isconservedbetweenzebrafishandhuman.Conclusions.Ewsr1 maintainsmitoticintegrityandproneuralcellsurvivalinearlyzebrafishdevelopment. Citation: AzumaM,EmbreeLJ,SabaawyH,HicksteinDD(2007)EwingSarcomaProteinEwsr1MaintainsMitoticIntegrityandProneuralCellSurvival intheZebrafishEmbryo.PLoSONE2(10):e979.doi:10.1371/journal.pone.0000979 INTRODUCTION RESULTS TheEWSR1geneisinvolvedinanumberofdifferentsarcomasas a result of chromosomal translocations. EWSR1 is fused to an ETStranscriptionfactor(FLI-1,ERG,ETV-1,E1AForFEV)in Ewingsarcoma;toactivatingtranscriptionfactor-1(ATF-1)insoft tissue clear cell sarcoma; to Wilms