小鼠早期胚胎发育

小鼠早期胚胎发育景乃禾中国科学院上海生物化学与细胞生物学研究所体轴形成和原肠运动Axisformation&Gastrulation小鼠早期胚胎发育EarlymousedevelopmentPreimplantationPostimplantationEarlymousedevelopment(early)Epiblast(late)EpiblastAnteriorneuroectodermVE:visceralendodermAVE:anteriorVEDVE:distalVECelllineagesinearlymouseembryoMorulaInnerCellMassTrophectodermPrimitiveendodermEpiblastParietalendodermVisceralendodermDefinitiveendodermMesodermEctodermMesendodermCNSEpidermisMouseembryodevelopmentfromfertilizationtogastrulationDevelopment139,3-14,2012？？？TwopossiblemechanismsforthegenerationofmultiplecelltypesandpolarityDevelopment139,3-14,2012DevCell16,398-410,2009MousetrophectodermdistinguishfrominnercellmassregulatedbyHipposignalingpathwayCellposition-dependentdifferentiationmediatedbyHipposignalingDevelopment139,3-14,2012MouseembryodevelopmentfromfertilizationtogastrulationDevelopment139,3-14,2012？EarlymousedevelopmentE3.5E4.5ICM‘‘SaltandPepper’’expressionofNanogandGata6intheICMofE3.5blastocystsDevCell10,615-624,2006SegregationandrelocationofepiblastandPrEcellsDevelopment139,3-14,2012MouseembryodevelopmentfromfertilizationtogastrulationDevelopment139,3-14,2012？Emergingasymmetryandestablishmentofanterior-posteriorpolarityintheE5.75mouseembryoAxisofAnterior-PosteriorAxisofProximal&DistalDistalVEtoAVECellmovementsinearlymouseembryosEpiblasttoposteriorExtraembryonicectodermtoposteriorepiblastEpiblasttoposteriorOtx2VEcis-lacZ5.5dpc5.75dpc6.25dpc6.0dpcOtx2KI-lacZMovementofOtx2-positivecellsfromDVEtoAVEDVE:distalvisceralendoderm;AVE:anteriorvisceralendodermAsymmetricexpressionofLefty1transgenesinperi-implantationmouseembryosDevCell10,451-459,2006TwotypesofLefty1+cellinmouseembryosbetweenE3.5andE4.5NatCellBiol13,743-752,2011DistinctoriginsofDVEandAVENatCellBiol13,743-752,2011OriginsofthedorsalandanteriorvisceralendodermDevelopment139,3-14,2012SignalingpathwaysinvolvedinA-PaxisdeterminationDevelopment139,3-14,2012MouseembryodevelopmentfromfertilizationtogastrulationDevelopment139,3-14,2012NervoussystemSkinandhairHeartMuscleliverLungs…………Earlymouseembryodevelopmentandlineagesegregation3.5dpcICM4.5dpcearlyepiblast5.5dpclateepiblast6.5dpcPrimitivestreakRapidproliferationduringgastrulation:dramaticsignalingandgeneexpressionchangesFossat,N.,etal.(2012)CellCycle11:26-32“Itisnotbirth,marriage,ordeath,butgastrulation,whichistrulythemostimportanttimeinyourlife.”LewisWolpert,1986VE:visceralendodermAVE:anteriorVEDVE:distalVEPrimitivestreakformationPS:PrimitiveStreakEMTatmouseprimitivestreakEMTatmouseprimitivestreakEpiblastPrimitveStreakNascentMesodermCellAdhesion&Migration4:3,447-457MousegastrulationandgermlayerformationCell132,661–680,2008MyocardinE7.5E8.5LatemousedevelopmentAxisofDorsal-VentralCelllineagesinearlymouseembryoEmbryoculturesystemfortime-lapsemovieacquisitionofnodemorphogenesisDevCell13,884-896,2007invitroembryocultureGFPknock-intracingTime-lapseimagesofnodemorphogenesisNoto-DevCell13,884-896,2007ThedisplacementmodelofendodermmorphogenesisinthemousegastrulaThedispersalmodelofendodermmorphogenesisinthemousegastrulaVisceralendoderm-derivedcellsareincorporatedintotheguttube12–18somiteembryosrevealedthepresenceofAfp-GFP+cellsintheguttubeThiswasnotnewexpressionofthetransgene,asGFPmRNAcouldonlybedetectedintheyolksacatthisstageThesevisceralendodermderivedcellscontinuetodivideandareeventuallyincorporatedintotheepitheliumoftheguttubeDevCell15,509-520,2008CelllineagesinearlymouseembryoDefinitiveendodermMesodermEctodermMesendodermCNSEpidermisEpiblastCelllineageinearlymouseembryoE7.0TEctodermMesendodermBraWnt3E7.5MesendodermmarkersGeneexpressionandregionalizedallocationoftissueprogenitorsAxialmesodermDefinitiveendodermParaxialmesodermLateralplatemesodermExtraembryonicmesodermNeuroectoderm?ThemarkersofgermlayersDefinitiveendodermMesodermEctodermMesendodermNeuralEpidermisNkx2.5Sox17Nodal,T,Wnt3,GscEpiblastMesp1Mixl1Flk1Gata4Gata6Foxa2Sox1Pax6NestinSix3Ck5Ck8Ck18Zo-1FGF5,NodalFate-mappingofthedistalcapepiblastbycarbocyaninedyelabelingE6.5DyeinjectionThedistalcapepiblastcellsmigratetotheanteriorneuroectodermDevelopment,107,55-67(1989)Magazine105Figure1Fatemapsforembryosoffourvertebratespecies,drawnwiththeirnormaltopography(seetextforfurtherdetails).(a)Appearanceofeachembryobeforegastrulation.Scalebars:fish,500–600mm;frog1–2mm;chick,2-3mm;mouse,700mm.(b)Fatemapsatearlygastrulation,drawninnormaltopography.Embryosarealignedsothatthe‘organizer’isontherighthandsideofeachfatemap.Theorganizerisfoundinthe‘embryonicshield’(SH)ofthezebrafishandthe‘dorsalblastoporelip’(BL)ofthefrogembryo;theprecursoroftheorganizer(thenode)isfirstfoundasanintegralpartoftheearlyprimitivestreak(PS),thefirstmorphologicallandmarkofthechickormouseembryo.Inrepresentingthechickembryo,separateimagesofablasto-dermareshowntoindicategermlayerprecursorswithoverlappingdistributions.(c)Fatemapsfortheectodermallayersattheendofgastrulation(mesodermalandendodermallayersarenotshownduetospaceconstraints).Theanterior–posterioraxesarealignedhorizontallyinthefigure,suchthatthethesiteofcellmovementtotheinteriorisontheposterior(righthands