小鼠早期胚胎发育

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:

2、 distal VECell lineages in early mouse embryoMorulaInner Cell MassTrophectodermPrimitive endodermEpiblastParietal endodermVisceral endodermDefinitive endodermMesodermEctodermMesendodermCNSEpidermisMouse embryo development from fertilization to gastrulationDevelopment 139, 3-14, 2012？Two possible mec

3、hanisms for the 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, 2012M

4、ouse embryo development 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, 20

5、12Mouse embryo development 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 t

6、o posteriorExtraembryonic ectoderm 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-implan

7、tation mouse embryosDev Cell 10, 451-459, 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

8、 involved in A-P axis determinationDevelopment 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 epibl

9、ast6.5dpcPrimitive streakRapid proliferation during 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

10、 endodermAVE: anterior VEDVE: distal VEPrimitive streak formation 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, 2008MyocardinE

11、7.5E7.5E8.5E8.5Late mouse developmentAxis of Dorsal-VentralCell lineages in 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

12、-896, 2007The displacement model of endoderm morphogenesis in the mouse gastrulaThe 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

13、new expression of the transgene, as GFP mRNA could only be detectedin the yolk 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 endodermM

14、esodermEctodermMesendodermCNSEpidermisEpiblastCell lineage in early mouse embryoE7.0TEctodermMesendodermBraWnt3E7.5Mesendoderm markers Gene expression and regionalized allocation of tissue progenitorsAxial mesodermDefinitive endodermParaxial mesodermLateral plate mesodermExtraembryonic mesodermNeuro

15、ectoderm?The markers of germ layersDefinitive endodermMesodermEctodermMesendodermNeuralEpidermisNkx2.5Sox17Nodal, T, Wnt3, GscEpiblastMesp1Mixl1Flk1Gata4Gata6Foxa2Sox1Pax6NestinSix3Ck5Ck8Ck18Zo-1FGF5, NodalFate-mapping of the distal cap epiblast by carbocyanine dye labelingE6.5Dye injectionThe dista

16、l cap epiblast cells migrate to the anterior neuroectoderm Development, 107, 55-67 (1989)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. Sc

17、al 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 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 at e map.Theorgani zer i s f ound i n t he embryoni c shi el d(SH)

18、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 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

19、 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 overl 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 a

20、nt 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 movement 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 rem

21、i 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, neuroect 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

22、; 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 oderm; exm, ext raembryoni cmesoderm.Fi shFrogChi ckM ouseAnimal pol eAnimal pol eProximalVegetal pol eVegetal pol eDi st alBl ast ocoelBl ast odermB

23、l 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 13St 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

24、oderm M esoderm Endoderm Organi zer Yol k Ext raembr yoni c t i ssues 1996 Cur rent Bi ol ogysesepxmlmhtexmamnendPSPSendendndneneneyol ksesesepxmpxmhthtlmblblndBLlmlmsmhmhtndSHexmendf bf bmbsehbscscNPSexmlmpxmscscsesehbhbmbmbf bf bmbhbpxmndNlmPSexmendM agazi ne105Fi gure 1Fate maps f or embryos of f

25、 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 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 opogra

26、phy.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 i sh and t he dorsalbl ast opore l i p (BL) of t he f rog embryo; t heprecursor of t he organi zer (t he node) i s f i rstf ound

27、as an i ntegral 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 embryo, separate images of a bl ast o-derm are show n t o i ndi cate germ l ayerprecursors w i t h overl appi ng di st ri but i ons. (c)Fa

28、te 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 anteri or posteri or axes areal i gned hori zontal l y i n t he f i gure, such t hat t het he si te of cel l movement t o t he i nteri or i s ont he

29、posteri 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 anteri 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, neuroect oderm, f b, f orebrai n; mb,

30、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 ateral mesoderm; nd, not ochord;ht , heart ; bl , bl ood. Endodermal t i ssues: end,gut endoderm. Ext raembryoni c t i ssues: am,amni on ect oderm;

31、 exm, ext raembryoni cmesoderm.Fi shFrogChi ckM ouseAnimal pol eAnimal pol eProximalVegetal pol eVegetal pol eDi stalBl 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 13St

32、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

33、ndBLlmlmsmhmhtndSHexmendf bf bmbsehbscscNPSexmlmpxmscscsesehbhbmbmbf bf bmbhbpxmndNlmPSexmendM agazine105Fi 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. Sca

34、l 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

35、t he zebraf i sh and t he dorsalbl ast opore l i p (BL) of t he f rog embryo; t heprecursor of t he organi zer (t he node) i s f i rstf ound as an i ntegral 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

36、ck embryo, separate images of a bl ast o-derm are show n t o i ndi cate germ l ayerprecursors w i t h overl appi ng di st ri but i ons. (c)Fate maps f or t he ect odermal l ayers at t he endof gast rul at i on (mesodermal and endodermall ayers are not show n due t o spaceconst rai nt s). The anteri

37、or posteri or axes areal i gned hori zontal l y i n t he f i gure, such t hat t het he si te of cel l movement t o t he i nteri or i s ont he posteri 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 anteri or ext remi t y of t he

38、primi 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, neuroect 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 atera

39、l mesoderm; nd, not ochord;ht , heart ; bl , bl ood. Endodermal t i ssues: end,gut endoderm. Ext raembryoni c t i ssues: am,amni on ect oderm; exm, ext raembryoni cmesoderm.Fi shFrogChi ckM ouseAnimal pol eAnimal pol eProximalVegetal pol eVegetal pol eDi stalBl ast ocoelBl ast odermBl ast odermEpi b

40、l 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 aStage 12. 5 13Stage XI V600 700 cel l s i n epi bl astStage 56. 5 days post coi t um650 cel l s i n epi bl ast7. 5 days post coi t umYol kEarl y embryo Ect oderm M esoderm Endo

41、derm Organi zer Yol k Ext raembryoni c t i ssues 1996 Current Bi ol ogysesepxmlmhtexmamnendPSPSendendndneneneyol ksesesepxmpxmhthtlmblblndBLlmlmsmhmhtndSHexmendf bf bmbsehbscscNPSexmlmpxmscscsesehbhbmbmbf bf bmbhbpxmndNlmPSexmendCurrent Biology 1996, Vol 6 No 2Fate maps for the ectodermal layer M ag

42、azi ne105Figure 1Fate maps f or embryos of f our vertebratespeci es, draw n 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 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

43、ygast rul at i on, drawn 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 i sh and t he dorsalbl ast opore l i p (BL) of t he f rog embryo; t heprecursor of t

44、he organi zer (t he node) i s f i rstf ound as an i ntegral 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 embryo, separate images of a bl ast o-derm are show n t o i ndi cate germ l ayerprecursors w i

45、 t h overl appi ng di st ri but i ons. (c)Fate maps f or t he ect odermal l ayers at t he endof gast rul at i on (mesodermal and endodermall ayers are not show n due t o spaceconst rai nt s). The anteri or posteri or axes areal i gned hori zontal l y i n t he f i gure, such t hat t het he si te of c

46、el l movement t o t he i nteri or i s ont he posteri 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 anteri 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 ssu

47、es: ne, neuroect 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 ateral mesoderm; nd, not ochord;ht , heart ; bl , bl ood. Endodermal t i ssues: end,gut endoderm. Ext

48、raembryoni c t i ssues: am,amni on ect 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 ySt age 10

49、+5000 cel l s i n bl ast ul aSt age 12. 5 13St 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 Current Bi ol ogysesepxmlmhtexmamnendPSPSendendndneneneyol ksesesepxmpxmhthtlmblblndBLlmlmsmhmhtndSHexmendf bf bmbsehbscscNPSexmlmpxmscscsesehbhbmbmbf bf bmbhbpxmndNlmPSexmendWheat germ agglutinin (WGA)D