Exogenous Amino Acids Regulate Trophectoderm Differentiation in the Mouse Blastocyst through an mTOR-Dependent Pathway

Developmental Biology

Patrick M. Martin¹  Ann E. Sutherland¹ 

[1] Department of Cell Biology, University of Virginia, Charlottesville, Virginia, 22908

关键词: mouse;    trophectoderm;    trophoblast;    amino acids;    mTOR;    rapamycin;    differentiation;    p70S6 kinase;   

DOI  :  10.1006/dbio.2001.0461

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Atthelateblastocyststage,theepithelialtrophectodermcellsofthemammalianembryoundergoaphenotypicchangethatallowsthemtoinvadeintotheuterinestromaandmakecontactwiththematernalcirculation.Thisstepcanberegulatedinvitrobytheavailabilityofaminoacids.Embryosculturedindefinedmediumlackingaminoacidscannotformtrophoblastcelloutgrowthsonfibronectin,aninvitromodelofimplantation,butremainviableforupto3daysincultureandwillformoutgrowthswhentransferredintocompletemedium.Theaminoacidrequirementisadevelopmentallyregulatedpermissiveeventthatoccursduringa4-to8-hperiodattheearlyblastocyststage.Aminoacidsaffectspreadingcompetencespecificallybyregulatingtheonsetofprotrusiveactivityandnottheonsetofintegrinactivation.Rapamycin,aspecificinhibitorofthekinasemTOR/FRAP/RAFT1,blocksaminoacidstimulationofembryooutgrowth,demonstratingthatmTORisrequiredfortheinitiationoftrophectodermprotrusiveactivity.Inhibitionofglobalproteintranslationwithcycloheximidealsoinhibitsaminoacid-dependentsignals,suggestingthatmTORregulatesthetranslationofproteinsrequiredfortrophoblastdifferentiation.OurdatasuggestthatmTORactivityhasadevelopmentalregulatoryfunctionintrophectodermdifferentiationthatmayservetocoordinateembryoanduterusatthetimeofimplantation.

【 授权许可】

Unknown