A Role for Phosphoinositide 3-Kinase in the Control of Cell Division and Survival during Retinal Development

[摘要] Neurogenesisintheretinarequirestheconcertedactionofthreedifferentcellularprocesses:proliferation,differentiation,andapoptosis.ClassIAphosphoinositide3-kinase(PI3K)isaheterodimercomposedofap85regulatoryandap110catalyticsubunit.p110αhasbeenshowntoregulatecelldivisionandsurvival.Littleisknownofitsfunctionindevelopment,however,asp110αknockoutmiceexhibitCNSdefects,butdeathatearlyembryonicstagesimpairsfurtherstudy.Here,weexaminetheroleofPI3KinmouseretinadevelopmentbyexpressinganactivatingformofPI3Kregulatorysubunit,p65PI3K,asatransgeneintheretina.Miceexpressingp65PI3Kshowedseverelydisruptedretinamorphogenesis,withectopiccellmassesintheneuroepitheliumthatevolvedintoinfoldingsofadultretinalcelllayers.Thesechangescorrelatedwithanalteredcellproliferation/celldeathbalanceatearlydevelopmentalstages.Nonetheless,themostaffectedcelllayerinadultretinawasthatofphotoreceptors,whichcorrelatedwithselectivelyincreasedsurvivalofthesecellsatdevelopmentalstagesatwhichcelldivisionhasceased.TheseresultsdemonstratetherelevanceofaccuratePI3Kregulationfornormalretinaldevelopment,supportingclassIAPI3Kinvolvementininductionofcelldivisionatearlystagesofneurogenesis.Thesedataalsoshowthat,evenaftercelldivisiondecline,PI3Kactivationmediatessurvivalofdifferentiatedneuronsinvivo.

[学科分类] 生物科学（综合）

[关键词] retinal development;PI3K;signaling;proliferation;apoptosis;cell survival;neurogenesis;transgenic mice