Fertilizedone-cellstageegg(embryo),zonapellucidapresent(showninred).0-0.9dpc(range0-2.5)Scalebarinmicrons
TheilerStage2-Dividingegg
Dividingeggstage,zonapellucidapresent(showninred).Firstcleavageoccursatabout24hours.1dpc(range1-2.5)2-4cells.
Scalebarinmicrons
TheilerStage3-Morula
Four-to16-cellstageembryosfromearlytofullycompactedmorula.Zonapellucidapresent(showninred).Embryosintheoviducttowardsutero-tubaljunction.
2dpc(range1-3.5)4-16cells.
Allscalebarsinmicrons.
TheilerStage4-Blastocyst(ICMapparent)
Embryoprogressesfrommorulatotheblastocyststillwithinthezonapellucida(showninred).Thereisearlyevidenceoftheblastocoeliccavity.3dpc(range2-4)
16-40compactedcells.Allscalebarsinmicrons.
Intheblastocyststage(zona-intact)thereisadistinctinnercellmassandanouterlayerof
trophectodermcells.Usuallylocatedintheuterinelumen.
TheilerStage5-Blastocyst(zona-free)
Blastocyst(zona-free),invariablylocatedwithintheuterinelumen.4dpc(range3-5.5)Scalebarinmicrons
TheilerStage6-Attachmentofblastocyst
Blastocystsimplants,firstevidenceofembryonicendodermcellscoveringtheblastceolicsurfaceoftheinnercellmass.
4.5dpc(range4-5.5)WitschiStage8(rat)
CarnegieStage4(human)Scalebar
TheilerStage7-ImplantationandformationofEggCylinder
Ectoplacentalconeappears.Rapidincreaseinthenumberofinnercellmasscells
leadingtotheformationoftheepiblastwithsubsequentgrowthtoformtheeggcylinder.Theproximalorvisceralcells(oppositesidefromthetrophoblasticcap)arecuboidalinshape.Primaryendodermlinesthemuraltrophectoderm.5dpc(range4.5-6)WitschiStage10(rat)
CarnegieStage5(human)Scale
TheilerStage8-Differentiationofeggcylinder
Implantationsite2x3mm.Thematernaltissueisinvadedbytrophoblast(primary)giantcellsandtheectoplacentalconeisinvadedbymaternalblood.Differentiationoftheeggcylinderintoembryonicandextraembryonicregionsandtheformationoftheproamnioticcavity.Reichert'smembrane,whichisnon-cellularandsecretedbythedistalendodermfirstappears.6dpc(range5-6.5)
WitschiStage10-11(rat)CarnegieStage5(human)Scalebarinmicrons
TheilerStage9-AdvancedEndometrialReaction
PS:Advancedegg-cylinderstagewiththefirstevidenceofofanembryonicaxis.Thereisclearmorphologicaldistinctionbetweentheembryonicandextraembryonicectoderm.Theectoplacentalconeisfurtherinvadedbymaternalbloodandtheoriginallumenoftheuterinecrypthasdisappeared.
ES:Lateinthisstagegastrulationbegins,producingthefirstmesodermalcells.
6.5dpc(range6.25-7.25)
Downs&DaviesPS-ES:prestreaktoearlystreak
WitschiStage11(rat)
CarnegieStage6-7(human-stagetable)Scalebarinmicrons.
TheilerStage10-Amnion
Gastrulationcontinuesthroughoutallsub-divisionsofthisstageand:
MS:Tissueattheposteriorendoftheprimitivestreakbulgesintotheproamnioticcavityandformstheposterioramnioticfold.
LSOB:Inthemesodermoftheposterioramnioticfoldsmallcavitiescoalescetoformasinglecavity,theexocoelom.
LSEB:Theallantoicbudfirstappears,gastrulationcontinuesandthenodebecomesvisible.7dpc(range6.5-7.5)
Downs&DaviesMS-LSmidstreaktolatestreak
WitschiStage12(rat)
CarnegieStage8(human-stagetable)Scalebarinmicrons.
TheilerStage11-NeuralPlate,PresomiteStage
NP:Theamnioticcavityissealedoffwithnowthreecavities-amniotic,exocoelomand
ectoplacentalcleft.Theneuralplateisdefinedanteriorlyandtheheadprocessisdeveloping.Inthemidline,sub-adjacenttotheneuralgroove,thenotochodalplateisvisible.LNP:Theallantoicbudelongates.
EHF:Therostraloftheneuralplatebeginstoenlargetoformtheheadfolds.
LHF:Headfoldscontinuetoenlargeandtheforegutpocketbeginstoform.
7.5dpc(range(7.25-8)
Downs&DaviesOB-EB/LB-EHF-LHF:-noAll.budtolateAll.budtoearlyheadfoldtolateheadfold
WitschiStage12-13(rat)
CarnegieStage9(human-stagetable)Scalebarinmicrons.
TheilerStage12-Firstsomites
Unturnedembryowithfirstappearenceofsomitepairs.
1-4somites:Theallantoisextendsfurtherintotheexocoelomandthemaxiliarycomponentsofthe1st
branchialarchbecomeprominent.Thepreoticsulcusisvisibleinthe2-3
somiteembryo.Thecardiogenicplatebeginstoformandtheforegutpocketisclearlyvisible.
5-7:Theheadfoldsareparticularly
prominentandneuralclosureoccursintheregionofthe4thand5thsomites,extendinginbothdirectionsfromthissite.Theopticplacodesarefirstevidentandbecomeindentedtoformtheopticpits.Theheartrudimentdevelopsrapidly.Theallantoiscontactsthechorionattheendofthisstage.Absent:The2ndbranchialarchand>7somites.
8dpc(range7.5-8.75)1-7somitepairs
WitschiStage14-15(rat)
CarnegieStage9(human-stagetable)Allscalebarsinmicrons
Clickonanimageforalargerversion
TheilerStage13-Turningoftheembryo
Thisisashortperiodwithturninginitiatedinembryoswith6-8pairsofsomitesandusuallycompletedinembryoswith14-16pairsofsomites.Thefirstbranchialarchhas
maxillaryandmandibularcomponentsbutthemaxillaryprocessisnotvisibleuntillater(TS16).Asecondbranchialarchisnow
evident.Thereisevidenceofregionalisationoftheheartandtheneuraltubeisclosedfromapointoppositetheoutflowtracttotheproximalpartofthetail.Absent:3rdbranchialarch.
8.5dpc(range8-9.25)8-12somitepairs
WitschiStage15(rat)
CarnegieStage10(human-stagetable)Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheilerStage14-Formationandclosureofanteriorneuropore
Therostralextremityoftheneuraltubeclosesinembryoswithusuallyabout15-18somitepairsanddefinesthisstage.Theoticpitbecomesprogressivelymoreindentedbutnotclosed,themandibularprocessofthe1stbranchialarchisclearlyvisible.The3rdbranchialarchbecomesvisiblelateinthestage.Anincreasinglyprominentridgeonthelateralbodywall,
approximatelyatthelevelofthe8th-12thsomite,indicatesthesiteofthefutureforelimbbud.Absent:forelimbbud.
9dpc(range8.5-9.75)13-20somitepairsWitschiStage16(rat)
CarnegieStage11(human-stagetable)Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheilerStage15-Formationofposteriorneuropore;forelimbbud
Theposteriorneuroporeformandthe
condensationoftheforelimbbudbecomesapparentnearthe8th-12thsomitepairs.Adistinctcondensationofthehindlimbbudappearsjustattheendofthestage.Theforebrainvesiclesubdividesintotelencephalicanddiencephalicvesicles.Absent:hindlimbbud,Rathke'spouch.
9.5dpc(range9-10.25)21-29somitepairs
WitschiStage17-19(rat)
CarnegieStage12(human-stagetable)Allscalebarsinmicrons.
Clickonanimageforalargerversion
TheilerStage16-Closureofposteriorneuropore;hindlimbbudandtailbud
Thehindlimbbudbecomesvisibleatthelevelofthe23rd-28thsomites.Thetailbudappearsasashortstumpandthe3rdand4thbranchialarchesaredistinctlyconcave.Rathke'spouchandthenasalprocessesstarttoform.Attheendofthisstagetheposteriorneuroporebeginstoclose.Absent:thinandlongtail.
10dpc(range9.5-10.75)30-34somitepairs
WitschiStage20-21(rat)
CarnegieStage13(atlas),14(atlas),15(atlas)(human-stagetable)Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheilerStage17-Deeplensindentation
Themostobviousdistinguishing
featuresarethedeepeningofthelenspit,withanarrowingofit'souterpore-likeopening,andthefirstappearenceofthephysiologicalumbilicalhernia.The1stbranchialarchisconspicuouslydividedintoitmaxillaryandmandibular
components.Thereisadvanced
developmentofthebraintubeandthetailelongatesandthins.Absent:nasalpits.
10.5dpc(range10-11.25)35-39somitepairs
WitschiStage24-25(rat)
CarnegieStage13(atlas),14(atlas),15(atlas)(human-stagetable)Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheilerStage18-Closureoflensvesicle
Theprimaryexternallyrecognisablefeatureistheprogressiveclosureofthelensvesicle.Thesomitesinthecervicalregionarenolongervisibleandtherapidgrowthofthebrainisstriking.Thenasalpitsstarttoform.
Absent:auditoryhillocks,anteriorfootplate.
11dpc(range10.5-11.25)40-44somitepairs
WitschiStage25-26(rat)
CarnegieStage13(atlas),14(atlas),15(atlas)(human-stagetable)Allscalebarsinmicrons.
Clickonanimageforalargerversion
TheilerStage19-Lensvesiclecompletelyseparatedfromsurface
Thelensvesiclebecomescompletelyclosedanddetachedfromtheectoderm.Theperipheralmarginsoftheeyebecomewelldefined.Theforelimbsareseentobedividedintotworegions,theproximalpartconsistingofthefuture
limb-girdleandarmandthemoreperipheralpartwhichformsacircularorpaddle-shaped
handplate(anteriorfootplate).Themedialandlateralmarginsoftheoticpitarecomingtogetherreducingtheentrancetoanarrowslitandtheauditoryhillocksbecomevisible.
Absent:retinalpigmentation,signsoffingers.
11.5dpc(range11-12.25)45-47somitepairs
WitschiStage26-27(rat)
CarnegieStage16(atlas),(human-stagetable)Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheilerStage20-EarliestsignsoffingersPreviousStageStageIndexStageCriteriaAnatomyNextStageThehandplate(anteriorfootplate)isnolongercircularbutdevelopsangleswhichcorrespondtothefuturedigits.Theposteriorfootplateisalsodistinguishablefromthelowerpartoftheleg.Itispossibletoseethepigmentationofthepigmentedlayeroftheretinathroughthetransparentcornea.Thetongueandbrainvesiclesareclearlyvisible.
Absent:5rowsofwhiskers,indentedhandplate.
12dpc(range11.5-13)48-51somitepairsWitschiStage28(rat)
CarnegieStage17(atlas),(human-stagetable)
Allscalebarsinmicrons.
Clickonanimageforalargerversion
TheEdinburghMouseAtlas:TheilerStage21-AnteriorfootplateindentedPreviousStageStageIndexStageCriteriaAnatomyNextStageThedistalbordersoftheanteriorandposteriorfootplatesarenowindentedandthedigitwidthsandlocationscanbediscerned.Theelbowandwristarenowidentifiable.Thepinnarapidlydevelopsandformsacrestatrightanglestothehead.Fiverowsofvibrissaearevisibleaswellasaprominanthairfollicleovertheeyeandanotherovertheear.Thelensvesiclehaslostit'slumen.Thephysiologicalumbilicalherniaisprominent.Absent:hairfollicles,distallyseparatefingers.
13dpc(range12.5-14)52-55somitepairsWitschiStage29-30(rat)
CarnegieStage18(atlas),19(atlas),(human-stagetable)
Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheEdinburghMouseAtlas:TheilerStage22-FingersseparatedistallyPreviousStageStageIndexStageCriteriaAnatomyNextStageIndividualfingersarevisibleintheanteriorfootplateandtherearedeepindentationsbetweenthetoeswhicharenotyetseparated.Thelongbonesofthelimbsarepresentandtherearehairfolliclesinthepectoral,pelvicandtrunkregions.Thepinnaisturnedforwardsand
theumbilicalherniaisconspicuous.Absent:hairfolliclesinthecephalicregion.
14dpc(range13.5-15)56-~60somitepairsWitschiStage31(rat)
CarnegieStage20(atlas),21(atlas),22(atlas),23(atlas),(human-stagetable)
Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheEdinburghMouseAtlas:TheilerStage23-ToesseparatePreviousStageStageIndexStageCriteriaAnatomyNextStageThetoesseparateandareclearlydivergent,notbecomingparalleluntillater.Hairfolliclesarepresentinthecephalicregionbutnotattheperipheryofthevibrissae.Thepinnacoversmorethanhalfoftheexternalauditorymeatusandthe
eyelidsarestillopen.Absent:nailprimordia,fingers2-5parallel.
15dpc
>60somitepairsWitschiStage32(rat)Humanfoetalperiod.
Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheEdinburghMouseAtlas:TheilerStage24-RepositionofumbilicalherniaPreviousStageStageIndexStageCriteriaAnatomyNextStageFingers2-5arenearlyparallel.Nailprimordiaarevisibleonthetoes.Theeyelidshavefusedinmostcasesbytheendofthestageandthepinnaalmostcompletelycoverstheexternalauditorymeatus.Theumbilicalherniaisdisappearingandthereisacorrespondingincreaseinthesizeoftheperitonealsac.Absent:fingersandtoesjoinedtogether.
16dpc
>60SomitepairsWitschiStage33(rat)Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheEdinburghMouseAtlas:TheilerStage25-SkinwrinkledPreviousStageStageIndexStageCriteriaAnatomyNextStageTheskinhasthickenedandformedwrinklesandthesubcutaneousveinsarelessvisible.Thefingersandtoeshavebecomeparallelandtheumbilicalherniahasdisappeared.Theeylidshavefused.Whiskersarejustvisible.Absent:earextendingoverauditorymeatus,
longwhiskers.
17dpc
WitschiStage34(rat)Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheEdinburghMouseAtlas:TheilerStage26-LongwhiskersPreviousStageStageIndexStageCriteriaAnatomyNextStageThewhiskersvisibleatstage25aredefinitelylongerandtheskinhasthickened.Thepinnaislargerandsuchthatvirtuallynoneofthelumenoftheauditorymeatusisvisible.Theeyesarebarely
visiblethroughtheclosedeyelids
18dpc
Witschistage35(rat)Allscalebarsinmicrons.
Clickonanimageforalargerversion.
TheEdinburghMouseAtlas:TheilerStage27-NewbornmousePreviousStageStageIndexStageCriteriaAnatomyNextStageNewborn19-20dpc
Allscalebarsinmicrons.
Clickontheimageforalargerversion.
Mouseembryoscanbestagedaccordingtoavarietyofcriteria,themostgeneralofwhicharethosedescribedbyTheilerin\"TheHouseMouse:AtlasofMouseDevelopment\"(Springer-Verlag,NewYork,1989).Theiler'scriteriaaretoobroadtodistinguishmanyoftheimportantphasesofearlydevelopmentandmustthereforebesupplementedbyothers,forexample,cellnumber,somitenumberorthosecharcteristicsusedbyDownsandDavies(1993)Development,118,1255.Wehavethereforecombinedthesedifferentcriteriainthetable1belowwhichdefinesanewsetofstagesbasedonthenumberedTheilerseries,butwithintermediatedivisionsindicatedbynon-integerstagenumbers.Embryosofthesamegestationalagemaydifferintheirstageofdevelopment.Wehavethereforeincludedinthetableanindicationoftheexpectedrangeofgestationalages(daysofgestation,dpc)overwhicheachdevelopmentalstagemaybefound.Differentmousestrainsdevelopatdifferentratesand,insomecasesshowdifferencesintherelativeratesofdevelopmentofdifferentorgans.Strictly,thestagesrecognisedbyDownsandDaviesapplytooutbredmiceofthePOstrain.ThedataintheremainderofthetablebelowrefertoembryosofcrossesbetweenF1hybrid(C57BLXCBA)mice.
EachTheilerstageislinked(clickonthenumber)toitscorrespondingdiagram,withmoredetailsofthedefiningfeaturesforthatstage.Abrieftextorpictorialindextothediagramsisalsoprovided.
TheilerSomite
dpc(range)2
StageNo.312340-0.9(0-2.5)1
(1-2.5)2(1-3.5)3
Cell
(C57BLxCBA)F1mice4
number12-44-1616-40
One-celleggDividingeggMorulaBlastocyst,Innercellmassapparent
POmice5
(2-4)
54(3-5.5)4.5(4-5.5)
Blastocyst(zona-free)Attachmentofblastocyst,primaryendodermcoversblastocoelicsurfaceofinnercellmass
ImplantationandformationofeggcylinderEctoplacentalconeappears,enlargedepiblast,primaryendodermlinesmuraltrophectodermDifferentiationofeggcylinder.Implantationsites2x3mm.Ectoplacentalconeregioninvadedbymaternalblood,Reichert'smembraneandproamnioticcavityform
Pre-streak(PS),advancedendometrialreaction,ectoplacentalconeinvadedbyPSblood,extraembryonicectoderm,embryonicaxisvisible,Earlystreak(ES),gastrulationstarts,firstESevidenceofmesoderm7
(6.5-7.75)
Midstreak(MS),amnioticfoldstartsto
MS
form
Latestreak,nobud(LSOB),exocoelomLatestreak,earlybud(LSEB),allantoicbudfirstappears,node,amnionclosing
7.5(7.25-8)Neuralplate(NP),headdeveloping,amnioncompleteprocessOBLS
675(4.5-6)86
(5-6.5)
9a6.5(6.25-7.25)9b10a10b10c11a11b11c11d8
(7.5-8.75)
Lateneuralplate(LNP),elongatedallantoicEB/LBbudEarlyheadfold(EHF)Lateheadfold(LHF),foregutinvagination1-4somites,allantoisextends,1stbranchialarch,heartstartstoform,foregutpocketvisible,preoticsulcus(at2-3somitestage)
5-7somites,allantoiscontactschorionattheendofTS12
Absent2ndarch,>7somitesTurningoftheembryo,1stbranchialarchhasmaxillaryandmandibularcomponents,EHFLHF12a1-4
12b8.5(8-9.25)5-7
138-122ndarchpresent
Absent3rdbranchialarch9
(8.5-9.75)
Formation&closureofant.neuropore,oticpitindentedbutnotclosed,3rdbranchialarchvisibleAbsentforelimbbudFormationofpost.neuropore,forelimbbud,forebrainvesiclesubdividesAbsenthindlimbbud,Rathke'spouchPosteriorneuroporecloses,Formationofhindlimb&tailbuds,lensplate,Rathke'spouch;theindentednasalprocessesstarttoform
Absentthin&longtailDeeplensindentation,adv.devel.ofbraintube,tailelongatesandthins,umbilicalherniastartstoformAbsentnasalpitsClosureoflensvesicle,nasalpits,cervicalsomitesnolongervisible
Absentauditoryhillocks,anteriorfootplateLensvesiclecompletelyseparatedfromthesurfaceepithelium.Anterior,butnoposterior,footplate.AuditoryhillocksfirstvisibleAbsentretinalpigmentationandsignoffingersEarliestsignoffingers(splayed-out),posteriorfootplateapparent,retinapigmentationapparent,tonguewell-defined,brainvesiclesclear
Absent5rowsofwhiskers,indentedanteriorfootplateAnteriorfootplateindented,elbowandwristidentifiable,5rowsofwhiskers,umbilicalhernianowclearlyapparentAbsenthairfollicles,fingersseparatedistallyFingersseparatedistally,onlyindentationsbetweendigitsoftheposteriorfootplate,longbonesoflimbspresent,hairfolliclesinpectoral,pelvicandtrunkregions
1413-20
159.5(9-10.25)21-291610
(9.5-10.75)
30-34
1710.5(10-11.25)35-391811
40-44
(10.5-11.25)
1911.5(11-12.25)45-472012
(11.5-13)
48-51
2113(12.5-14)52-552214
(13.5-15)
56-~60
Absentopeneyelids,hairfolliclesincephalicregionFingers&Toesseparate,hairfolliclesalsoincephalicregionbutnotatperipheryofvibrissae,eyelidsopenAbsentnailprimordia,fingers2-5parallelRepositionofumbilicalhernia,eyelidsclosing,fingers2-5areparallel,nailprimordiavisibleontoes
Absentwrinkledskin,fingers&toesjoinedtogetherSkiniswrinkled,eyelidsareclosed,umbilicalherniaisgoneAbsentearextendingoverauditorymeatus,longwhiskersLongwhiskers,eyesbarelyvisiblethroughclosedeyelids,earcoversauditorymeatusNewbornMousePostnataldevelopment
23152416
251726272818191.Bard,J.B.L.,Kaufman,M.H.,Dubreuil,C.,Brune.R.M.,Burger,A.,Baldock,R.A.,Davidson,
D.R.(1998).Aninternet-accessibledatabaseofmousedevelopmentalanatomybasedonasystematicnomenclature.MechanismsofDevelopment74,111-20.
2.Dayspostconception,withthemorningafterthevaginalplugisfoundbeingdesignated
0.5dpc(orE0.5).FordetaileddiscussionseeKaufman(1994).TheAtlasofMouseDevelopment(2ndprinting),pp.515-525.London:AcademicPress.
3.Thefiguregivenreferstothenumberofthemostcaudalsomite.Noaccountistakenof
somitespartitioningintodermomyotomesandsclerotomes,noroftheirsubsequentdifferentiation.
4.AdaptedfromTheiler(1989)[TheHouseMouse:AtlasofEmbryonicDevelopment.New
York:Springer-Verlag]andKaufman(1994);detailedstagingforTheilerstages9-12courtesyofK.Lawson[personalcommunication].
5.FromDownes,K.M.andDavies,T.(1993).Stagingofgastrulatingmouseembryosby
morphologicallandmarksinthedissectingmicroscope.Development,118,1255-1266.
Comments
Generalcommentontiming(dpc):InjudgingthelowerandupperrangesofdpcequivalenttoaparticularTheilerstage,wehavegenerallyfollowedTheiler'sbookand,inmostcases,havegivenawiderrangethanTheiler,becausethenumbersofembryoshecitesaresmall.Wehavegivenalargerrangeatthemaximumthantheminimumbecause,ingeneral,embryosaremorelikelytoberetardedbytheirenvironmentorgeneticconstitutionthanmadetoproceedmorequicklythroughdevelopment.Inmostcases,however,theresultingdpcrangeisanestimatethatisconsistentwiththeresultsofTheiler,butnotbasedonadditionalevidence.
Commentonsomitenumbers:Therangeofsomitenumbersforeachstageisgivenonlyasaguidetowhatmightbeexpectedoftypicalembryos.AscanbeseenfromTheiler(1989)4thetrue
rangecanbemuchwider.Therefore,forallstagesafterTS12,thesomitenumbershouldnotbetakenasareliableglobalindicatoroftheoverallembryostage.
RichardBaldock,JonathanBard,DuncanDavidsonandKirstieLawson,7thMay1998PleasemailcommentstoProf.JonathanBard
因篇幅问题不能全部显示，请点此查看更多更全内容