Steroid Regulation of Midgut Cell Death during Drosophila Development

[摘要] Steroidhormonestriggerdynamictissuechangesduringanimaldevelopmentbyactivatingcellproliferation,celldifferentiation,andcelldeath.HerewecharacterizesteroidregulationofchangesinmidgutstructureduringtheonsetofDrosophilametamorphosis.Followinganincreaseinthesteroid20-hydroxyecdysone(ecdysone)attheendoflarvaldevelopment,futureadultmidgutepitheliumisformed,andthelarvalmidgutisrapidlydestroyed.Mutationsinthesteroid-regulatedgenesBR-CandE93differentiallyimpactlarvalmidgutcelldeathbutdonotaffecttheformationofadultmidgutepithelia.Incontrast,mutationsintheecdysone-regulatedE74AandE74Bgenesdonotappeartoperturbmidgutdevelopmentduringmetamorphosis.Larvalmidgutcellspossessvacuolesthatcontaincellularorganelles,indicatingthatthesecellsdiebyautophagy.WhilemutationsintheBR-C,E74,andE93genesdonotimpactDNAdegradationduringthiscelldeath,mutationsinBR-Cinhibitdestructionoflarvalmidgutstructures,includingtheproventriculusandgastriccaeca,andE93mutantsexhibitdecreasedformationofautophagicvacuoles.Dyingmidgutsexpresstherpr,hid,ark,dronc,andcrqcelldeathgenes,suggestingthatthecorecelldeathmachineryisinvolvedinlarvalmidgutcelldeath.Thetranscriptionofrpr,hid,andcrqarealteredinBR-Cmutants,andE93mutantspossessalteredtranscriptionofthecaspasedronc,providingamechanismforthedisruptionofmidgutcelldeathinthesemutantanimals.Thesestudiesindicatethatecdysonetriggersatwo-stephierarchycomposedofsteroid-inducedregulatorygenesandapoptosisgenesthat,inturn,regulatetheautophagicdeathofmidgutcellsduringdevelopment.

[学科分类] 生物科学（综合）

[关键词] steroid;ecdysone;programmed cell death;apoptosis;autophagy;development;metamorphosis;Drosophila