小鼠早期胚胎发育课件.ppt
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- 小鼠 早期 胚胎 发育 课件
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1、小鼠早期胚胎发育小鼠早期胚胎发育景乃禾景乃禾中国科学院上海生物化学与细胞生物学研究所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体轴形成和原肠运动Axis formation&Gastrulation小鼠早期胚胎发育小鼠早期胚胎发育Early mouse developmentPreimplantationPostimplantationEarly mouse development(early)Epiblast(late)EpiblastAnterior neuroectodermVE:visceral endodermAVE:anterior VEDVE:distal VEC
2、ell lineages in early mouse embryoMorulaInner Cell MassTrophectodermPrimitive endodermEpiblastParietal endodermVisceral endodermDefinitive endodermMesodermEctodermMesendodermCNSEpidermisMouse embryo development from fertilization to gastrulationDevelopment 139,3-14,2012?Two possible mechanisms for t
3、he generation of multiple cell types and polarityDevelopment 139,3-14,2012Dev Cell 16,398-410,2009Mouse trophectoderm distinguish from inner cell mass regulated by Hippo signaling pathway Cell position-dependent differentiation mediated by Hippo signalingDevelopment 139,3-14,2012Mouse embryo develop
4、ment from fertilization to gastrulationDevelopment 139,3-14,2012?Early mouse developmentE3.5E4.5ICMSalt and Pepper expression of Nanog and Gata6 in the ICM of E3.5 blastocystsDev Cell 10,615-624,2006Segregation and relocation of epiblast and PrE cells Development 139,3-14,2012Mouse embryo developmen
5、t from fertilization to gastrulationDevelopment 139,3-14,2012?Emerging asymmetry and establishment of anterior-posterior polarity in the E5.75 mouse embryoAxis of Anterior-PosteriorAxis of Proximal&DistalDistal VE to AVECell movements in early mouse embryosEpiblast to posteriorExtraembryonic ectoder
6、m to posterior epiblastEpiblast to posteriorOtx2 VEcis-lacZ5.5 dpc5.75 dpc6.25 dpc6.0 dpcOtx2 KI-lacZMovement of Otx2-positive cells from DVE to AVEDVE:distal visceral endoderm;AVE:anterior visceral endodermAsymmetric expression of Lefty1 transgenes in peri-implantation mouse embryosDev Cell 10,451-
7、459,2006Two types of Lefty1+cell in mouse embryos between E3.5 and E4.5Nat Cell Biol 13,743-752,2011Distinct origins of DVE and AVENat Cell Biol 13,743-752,2011Origins of the dorsal and anterior visceral endodermDevelopment 139,3-14,2012Signaling pathways involved in A-P axis determinationDevelopmen
8、t 139,3-14,2012Mouse embryo development from fertilization to gastrulationDevelopment 139,3-14,2012Nervous systemSkin and hairHeart Muscle liver Lungs Early mouse embryo development and lineage segregation3.5dpcICM 4.5dpcearly epiblast5.5dpclate epiblast6.5dpcPrimitive streakRapid proliferation duri
9、ng gastrulation:dramatic signaling and gene expression changes Fossat,N.,et al.(2012)Cell Cycle 11:26-32“It is not birth,marriage,or death,but gastrulation,which is truly the most important time in your life.”Lewis Wolpert,1986VE:visceral endodermAVE:anterior VEDVE:distal VEPrimitive streak formatio
10、n PS:Primitive StreakEMT at mouse primitive streakEMT at mouse primitive streakEpiblastPrimitve StreakNascent MesodermCell Adhesion&Migration 4:3,447-457Mouse gastrulation and germ layer formationCell 132,661680,2008MyocardinE7.5E7.5E8.5E8.5Late mouse developmentAxis of Dorsal-VentralCell lineages i
11、n early mouse embryoEmbryo culture system for time-lapse movie acquisition of node morphogenesisDev Cell 13,884-896,2007in vitro embryo cultureGFP knock-in tracing Time-lapse images of node morphogenesisNoto-Dev Cell 13,884-896,2007The displacement model of endoderm morphogenesis in the mouse gastru
12、laThe dispersal model of endoderm morphogenesis in the mouse gastrulaVisceral endoderm-derived cells are incorporated into the gut tube1218 somite embryos revealed the presence of Afp-GFP+cells in the gut tubeThis was not new expression of the transgene,as GFP mRNA could only be detectedin the yolk
13、sac at this stageThese visceral endoderm derived cells continue to divide and are eventually incorporatedinto the epithelium of the gut tubeDev Cell 15,509-520,2008Cell lineages in early mouse embryoDefinitive endodermMesodermEctodermMesendodermCNSEpidermisEpiblastCell lineage in early mouse embryoE
14、7.0TEctodermMesendodermBraWnt3E7.5Mesendoderm markers Gene expression and regionalized allocation of tissue progenitorsAxial mesodermDefinitive endodermParaxial mesodermLateral plate mesodermExtraembryonic mesodermNeuroectoderm?The markers of germ layersDefinitive endodermMesodermEctodermMesendoderm
15、NeuralEpidermisNkx2.5Sox17Nodal,T,Wnt3,GscEpiblastMesp1Mixl1Flk1Gata4Gata6Foxa2Sox1Pax6NestinSix3Ck5Ck8Ck18Zo-1FGF5,NodalFate-mapping of the distal cap epiblast by carbocyanine dye labelingE6.5Dye injectionThe distal cap epiblast cells migrate to the anterior neuroectoderm Development,107,55-67(1989
16、)M agazi ne105Fi gure 1Fat e maps f or embryos of f our vert ebratespeci es,drawn w i t h t hei r normal t opography(see t ext f or f urt her det ai l s).(a)Appearance ofeach embryo bef ore gast rul at i on.Scal e bars:f i sh,500 600 mm;f rog 1 2m m;chi ck,2-3m m;mouse,700 mm.(b)Fat e maps at earl y
17、gast rul at i on,draw n i n normal t opography.Embryos are al i gned so t hat t he organi zer i son t he ri ght hand si de of each f at e map.Theorgani zer i s f ound i n t he embryoni c shi el d(SH)of t he zebraf i sh and t he dorsalbl ast opore l i p (BL)of t he f rog embr yo;t heprecursor of t he
18、 organi zer(t he node)i s f i rstf ound as an i nt egral part of t he earl y primi t i vest reak(PS),t he f i rst morphol ogi cal l andmarkof t he chi ck or mouse embryo.I n represent i ngt he chi ck embr yo,separate images of a bl ast o-derm are show n t o i ndi cate germ l ayerprecursors w i t h o
19、verl appi ng di st ri but i ons.(c)Fat e maps f or t he ect odermal l ayers at t he endof gast rul at i on(mesodermal and endodermall ayers are not shown due t o spaceconst rai nt s).The ant eri or post eri or axes areal i gned hori zont al l y i n t he f i gure,such t hat t het he si t e of cel l m
20、ovement t o t he i nt eri or i s ont he post eri or(ri ght hand si de)of t he map.Byt hi s stage,t he organi zer i s morphol ogi cal l ydi st i ngui shabl e at t he ant eri or ext remi t y of t heprimi t i ve st reak(N),as t he H ensen s node(chi ck)or t he node(mouse).Ect odermalt i ssues:ne,neuroe
21、ct oderm,f b,f orebrai n;mb,mi dbrai n;hb,hi ndbrai n;sc,spi nal cord;se,surf ace ect oderm.M esodermalt i ssues:pxm,paraxi almesoderm;hm,head mesoderm;sm,somi tes;lm,l at eral mesoderm;nd,not ochord;ht,heart;bl,bl ood.Endodermal t i ssues:end,gut endoderm.Ext raembr yoni c t i ssues:am,amni on ect
22、oderm;exm,ext raembryoni cmesoderm.Fi shFrogChi ckM ouseAnimal pol eAnimal pol eProximalVegetal pol eVegetal pol eDi st alBl ast ocoelBl ast odermBl ast odermEpi bl astYol k cel l syol k(a)(c)(b)50%epi bol y8000 cel l s i n bl ast oderm90%epi bol yStage 10+5000 cel l s i n bl ast ul aSt age 12.5 13S
23、t age XI V600 700 cel l s i n epi bl astSt age 56.5 days post coi t um650 cel l s i n epi bl ast7.5 days post coi t umYol kEarl y embr yo Ect oderm M esoderm Endoderm Organi zer Yol k Ext raembr yoni c t i ssues 1996 Cur rent Bi ol ogysesepxmlmhtexmamnendPSPSendendndneneneyol ksesesepxmpxmhthtlmblbl
24、ndBLlmlmsmhmhtndSHexmendf bf bmbsehbscscNPSexmlmpxmscscsesehbhbmbmbf bf bmbhbpxmndNlmPSexmendM agazi ne105Fi gure 1Fate maps f or embryos of f our vertebratespeci es,drawn w i t h t hei r normal t opography(see text f or f urt her detai l s).(a)Appearance ofeach embryo bef ore gast rul at i on.Scal
25、e bars:f i sh,500 600 mm;f rog 1 2m m;chi ck,2-3m m;mouse,700 mm.(b)Fate maps at earl ygast rul at i on,draw n i n normal t opography.Embryos are al i gned so t hat t he organi zer i son t he ri ght hand si de of each f ate map.Theorgani zer i s f ound i n t he embryoni c shi el d(SH)of t he zebraf
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