TSC(tuberous sclerosis complex)在果繩生殖干細(xì)胞中的作用.pdf

1、碩士學(xué)位論文學(xué)校代碼：l0023學(xué)號(hào)：S2005505TSC(tuberoussclerosiscomplex)在杲蠅生殖干細(xì)胞中的作用所院：姓名：指導(dǎo)教師：導(dǎo)師小組：學(xué)科專業(yè)：研究方向：完成日期：北京生命科學(xué)研究所孫培郭巖襲榮文生物化學(xué)與分子生物學(xué)基因?qū)?dòng)物發(fā)育的影響2008年5月TheroleofTSC1／2一TORsignalingpathwayinD加sop歷Z腸germlinestemcellregulationAbstrac

2、tIntheD聊印辦f腸ovary，geⅡnlinestemcell(GSC)sel‘rene、valandmaintenanceisregulatedbybothintrinsicfactorsaIldfactorS舶mthenicheBMPsignalingactivatedbythenichesignalsregulatesGSCselfrenewalthroughdirectrepressionof6刪(6口gQ廠聊ar6彪s)

3、expression，aJldthereexistotherfaCtorsthatregulateGSCselfrenewalindependentof6口聊TSC(mberoussclerosiscomplex)isah啪aIldominantdisorder’whichiscausedbymutationsineitherof鉚ogenes，殆cJ，and乃以111mammala11dfmitnies，theirproduCtsTS

4、C1andTSC2fb肌acomplexwithGTPaSeactivities，、)~rhichrepresstheactiVit)rof1’oR(targertofrap鋤ycin)，throughasmallGproteiIl，Rheb(I己硒homologenrichedi11brain)TORisaSer／『Thrkinase，whichisconserVed行omyeaSttomammal，andfhnctionsin錒oc

5、omplexesOneofthecomplexes，1DRClsensestheenViroIlIIlentalsignals，mailllythroughTSCl／2，aI：IdregulatesceUgr0、礬handmetabolismInourstudy，、VefouIldmatTSCl／2ToRClsignalingalsoregulatesGSCmaintainanceaIlddifrerentiationthroughmo

6、dulatingBMP6繃signalingand6口聊iIldependentmachenisms乃c，力mutationsleadtoGSCrapidlossbydi廊rentiation，aIldin乃cJmut鋤tGSC，BMPsigIlalingactiV時(shí)issignificantlydo、Ⅳn—regulated，butthereisnotadistinguishableupregulationof6口柳expressio

7、nFurthemore，6口朋mutationcouldnotrescuemeGSClosscausedby乃c』mutation，arld豇cJ6口mdouble刪ltantge肌cellscoulddi腩rentiateintoe砌ycyst，indicatingthatTSCl／2alsoregulateGSCmaintainanceindependentof6口腳Feedingtheflieswimrap鋤ycin，觚inhib

8、itorofToRCl，couldrescuetheGSCloss，thedownregulationofBMPsigIlalingcausedby西c，mutation，嬲well器thedi虢rentiationof始cJ6a所doublemutantgenncells，indicatingthattllephenotypescausedby始c』／2mutationsisaresultofhyperactiVationofTORC

9、1EliminationofS6K，adoWnstre鋤targetofToRC1，canalsocompletelyrescuetheGSClosscausedby磚以mutalltion，fWtIlersupportingthatTORC1isthedo、ⅣnstreamofTSCl／2insuppressingGSCprematuredi疏rentiation乃，a11dSZⅨ。mutantGSCshowednormalmaime