發(fā)育生物學(xué)——體軸與胚層

1、哺乳動(dòng)物胚軸形成與胚層分化哺乳動(dòng)物胚軸形成與胚層分化l Vertebrate embryos show differences in form before gastrulation l After gastrulation, rather similar at Phylotypic stage (種系型種系型期期): head structure, neural tube, notochord, somitesLife cycle of the mousel 9 weeksl fertilization in the oviduct, meiois II completedl clevage

2、 morula卵裂卵裂蛙的早期卵裂。蛙的早期卵裂。 A 第一次卵裂，第一次卵裂， B 第二次卵裂，第二次卵裂， C 第四次卵裂，動(dòng)物極和植第四次卵裂，動(dòng)物極和植物極細(xì)胞出現(xiàn)差異。物極細(xì)胞出現(xiàn)差異。卵裂期是指受精卵開始有絲分裂并產(chǎn)生由較小的細(xì)胞構(gòu)成的囊胚卵裂期是指受精卵開始有絲分裂并產(chǎn)生由較小的細(xì)胞構(gòu)成的囊胚(blastula) (blastula) 的過程。主要特點(diǎn)包括：的過程。主要特點(diǎn)包括：l 分裂周期短分裂周期短; ;l 分裂球的體積下降：海膽胚胎的質(zhì)分裂球的體積下降：海膽胚胎的質(zhì)/ /核核比由比由550550降至降至6 6; ;l 早期卵裂中合子基因大多處于休眠狀態(tài)；早期卵裂中合子基因大

3、多處于休眠狀態(tài)；l 卵裂常經(jīng)歷由均等裂向不均等裂變化。卵裂常經(jīng)歷由均等裂向不均等裂變化。3. hatching1. compaction2. blastocyst cavity formationgene expression starts128 cellDay 7-humanDay 5.5-mouse哺乳動(dòng)物的早期卵裂發(fā)生在輸卵管中哺乳動(dòng)物的早期卵裂發(fā)生在輸卵管中Mouse pre-implantation stages: cleavage, compaction, blastocyst cavity formationCompaction at the late 8-cell stage,

4、 With apical-basal polarization of cells128-cell blastocystcompaction128-cell blastocystl 緊密化緊密化(Compaction): 8細(xì)胞分裂后不久，卵裂球突然擠在一細(xì)胞分裂后不久，卵裂球突然擠在一起，卵裂球之間的接觸面增大，形成一個(gè)緊密的細(xì)胞球體。起，卵裂球之間的接觸面增大，形成一個(gè)緊密的細(xì)胞球體。哺乳動(dòng)物卵裂球的哺乳動(dòng)物卵裂球的compaction: 發(fā)生第三次卵裂后不久發(fā)生第三次卵裂后不久 小鼠小鼠8細(xì)胞胚胎細(xì)胞胚胎compaction前后前后小鼠桑椹胚的壓縮現(xiàn)象小鼠桑椹胚的壓縮現(xiàn)象 8 8細(xì)胞時(shí)期，

5、小鼠細(xì)胞表面光滑，微絨細(xì)胞時(shí)期，小鼠細(xì)胞表面光滑，微絨毛均勻分布，壓縮后微絨毛僅分布于細(xì)胞的外表面，細(xì)胞之間的毛均勻分布，壓縮后微絨毛僅分布于細(xì)胞的外表面，細(xì)胞之間的聯(lián)系加強(qiáng)了。聯(lián)系加強(qiáng)了。未壓縮的和壓縮的未壓縮的和壓縮的8細(xì)胞小鼠胚胎的比較細(xì)胞小鼠胚胎的比較Compaction的機(jī)制的機(jī)制: 8細(xì)胞胚胎的外層胞間形成細(xì)胞胚胎的外層胞間形成致密連接致密連接 (tight junctions)，可將球內(nèi)部，可將球內(nèi)部的細(xì)胞與外環(huán)境隔絕，起的細(xì)胞與外環(huán)境隔絕，起穩(wěn)定細(xì)胞球的作用。穩(wěn)定細(xì)胞球的作用。而內(nèi)而內(nèi)層胞間形成縫隙連接層胞間形成縫隙連接 (gap junction)，可以交換小分，可以交換小分

6、子和離子。子和離子。 注射注射E-Cadherin抗體的胚胎不能夠致密化。抗體的胚胎不能夠致密化。 在在4細(xì)胞期激細(xì)胞期激活蛋白激酶活蛋白激酶C導(dǎo)致導(dǎo)致compaction發(fā)生。因此，發(fā)生。因此，Compaction可能可能始于蛋白激酶始于蛋白激酶C的活化，它引起細(xì)胞骨架的重排，在膜上均勻分的活化，它引起細(xì)胞骨架的重排，在膜上均勻分布的布的E-Cadherin重新定位在胞間相交處。重新定位在胞間相交處。哺乳動(dòng)物囊胚細(xì)胞命運(yùn)的早期分化位置決定論哺乳動(dòng)物囊胚細(xì)胞命運(yùn)的早期分化位置決定論l 16細(xì)胞期桑椹胚(morula):位于內(nèi)部的少數(shù)細(xì)胞產(chǎn)生的子細(xì)胞將組成內(nèi)細(xì)胞團(tuán)(inner cell mass

7、)，而位于外部的細(xì)胞產(chǎn)生的子細(xì)胞大多構(gòu)成滋養(yǎng)外胚層(trophoblast)。l 32細(xì)胞期胚泡(blastocyst):位于囊胚腔一端的內(nèi)細(xì)胞團(tuán)(約10個(gè)細(xì)胞)將發(fā)育胚胎的本體及與其相連的卵黃囊、尿囊和羊膜；外層的滋胚層生成絨毛膜，為胎兒從母體攝取營(yíng)養(yǎng)物質(zhì)和氧，并產(chǎn)生激素以避免母體的排斥反應(yīng)。 內(nèi)細(xì)胞團(tuán)的產(chǎn)生是哺乳動(dòng)物早期發(fā)育的關(guān)鍵步內(nèi)細(xì)胞團(tuán)的產(chǎn)生是哺乳動(dòng)物早期發(fā)育的關(guān)鍵步驟之一。驟之一。通過對(duì)活體胚胎的觀察研究，發(fā)現(xiàn)這通過對(duì)活體胚胎的觀察研究，發(fā)現(xiàn)這種重要決定作用僅僅依賴于細(xì)胞于某一正確時(shí)種重要決定作用僅僅依賴于細(xì)胞于某一正確時(shí)間出現(xiàn)在某一正確的位置。間出現(xiàn)在某一正確的位置。壓縮后位于外層

8、的壓縮后位于外層的細(xì)胞將形成滋養(yǎng)層細(xì)胞，而內(nèi)部的細(xì)胞將發(fā)育細(xì)胞將形成滋養(yǎng)層細(xì)胞，而內(nèi)部的細(xì)胞將發(fā)育成胚胎。成胚胎。 一個(gè)細(xì)胞是否成為胚胎或滋養(yǎng)層細(xì)胞，完全取一個(gè)細(xì)胞是否成為胚胎或滋養(yǎng)層細(xì)胞，完全取決于壓縮作用后決于壓縮作用后細(xì)胞所處的位置細(xì)胞所處的位置是位于外周還是位于外周還是內(nèi)部。是內(nèi)部。哺乳動(dòng)物胚泡的著床哺乳動(dòng)物胚泡的著床l 胚泡在向子宮移動(dòng)過程中體積增大，是由定位于滋胚層細(xì)胞胚泡在向子宮移動(dòng)過程中體積增大，是由定位于滋胚層細(xì)胞膜囊胚腔一側(cè)的膜囊胚腔一側(cè)的NaK泵將外部泵將外部Na+泵入腔中，最后通過滲透泵入腔中，最后通過滲透作用吸水使囊胚腔增大。作用吸水使囊胚腔增大。 隨著囊胚腔內(nèi)離子濃

9、度的增加，水分就通過滲透作用進(jìn)入進(jìn)入囊胚腔內(nèi)。囊胚隨著囊胚腔內(nèi)離子濃度的增加，水分就通過滲透作用進(jìn)入進(jìn)入囊胚腔內(nèi)。囊胚腔內(nèi)液體的積累對(duì)囊胚腔壁造成一個(gè)向外的壓力，這種靜水壓是參與形成和維持腔內(nèi)液體的積累對(duì)囊胚腔壁造成一個(gè)向外的壓力，這種靜水壓是參與形成和維持囊胚為球形的一個(gè)重要作用力。囊胚為球形的一個(gè)重要作用力。 哺乳動(dòng)物胚泡的著床哺乳動(dòng)物胚泡的著床l 胚胎外的胚胎外的透明帶透明帶阻止了胚泡與輸卵管壁的粘連阻止了胚泡與輸卵管壁的粘連-異位妊娠。異位妊娠。l 胚泡到達(dá)子宮時(shí)，胚胎細(xì)胞分泌胚泡到達(dá)子宮時(shí)，胚胎細(xì)胞分泌Strypsin（一種類胰蛋白酶一種類胰蛋白酶)，它使透明帶穿孔，胚泡從孔中，它使

10、透明帶穿孔，胚泡從孔中“孵化孵化” (hatch) 出與子宮壁出與子宮壁接觸，通過一系列反應(yīng)而著床。接觸，通過一系列反應(yīng)而著床。人類的同卵雙生的發(fā)生人類的同卵雙生的發(fā)生(占出生總數(shù)的占出生總數(shù)的0.25%)分離分離發(fā)生在發(fā)生在滋胚層形成前滋胚層形成前(約受精后約受精后5天前天前)的分割，有的分割，有獨(dú)立的絨毛膜和羊膜。占同獨(dú)立的絨毛膜和羊膜。占同卵雙生的卵雙生的33%。發(fā)生在發(fā)生在滋胚層形成后但羊膜滋胚層形成后但羊膜形成前形成前(約受精后約受精后59天天)的的分割，共用絨毛膜，有獨(dú)立分割，共用絨毛膜，有獨(dú)立的羊膜。占同卵雙生的的羊膜。占同卵雙生的66%發(fā)生在發(fā)生在羊膜形成后羊膜形成后(約受精約

11、受精9天后天后)的分割，共用絨毛膜的分割，共用絨毛膜和羊膜，易出現(xiàn)連體兒。和羊膜，易出現(xiàn)連體兒。人類的連體嬰兒人類的連體嬰兒l 嵌合胚嵌合胚：早期卵裂球早期卵裂球有同等的發(fā)育潛力。自然有同等的發(fā)育潛力。自然人群中也出現(xiàn)過同時(shí)有人群中也出現(xiàn)過同時(shí)有XX型和型和XY型細(xì)胞的人，型細(xì)胞的人，異卵雙生的兩個(gè)胚胎融合異卵雙生的兩個(gè)胚胎融合形成的單一混合個(gè)體。形成的單一混合個(gè)體。l 胚胎干細(xì)胞胚胎干細(xì)胞：保持了保持了分化為胚胎本體的潛能的分化為胚胎本體的潛能的、可在體外增殖的胚胎細(xì)、可在體外增殖的胚胎細(xì)胞。在基因功能研究和疾胞。在基因功能研究和疾病治療方面有重要的作用病治療方面有重要的作用。哺乳動(dòng)物中的嵌

12、合胚、胚胎干細(xì)胞哺乳動(dòng)物中的嵌合胚、胚胎干細(xì)胞l 人工受精人工受精：如主要：如主要用于治療不育癥、保用于治療不育癥、保存存 和運(yùn)輸優(yōu)良個(gè)體。和運(yùn)輸優(yōu)良個(gè)體。l 胚胎切割胚胎切割：在：在2 24 4細(xì)胞期分割胚胎細(xì)胞細(xì)胞期分割胚胎細(xì)胞，用于繁殖優(yōu)良家畜，用于繁殖優(yōu)良家畜個(gè)體。個(gè)體。哺乳動(dòng)物中的人工受精和胚胎切割哺乳動(dòng)物中的人工受精和胚胎切割原腸作用原腸作用 Gastrulationl 原腸作用原腸作用是指囊胚細(xì)胞有規(guī)則的移動(dòng)，使細(xì)胞重新排是指囊胚細(xì)胞有規(guī)則的移動(dòng)，使細(xì)胞重新排列，用來形成內(nèi)胚層和中胚層器官的細(xì)胞遷入胚胎內(nèi)部列，用來形成內(nèi)胚層和中胚層器官的細(xì)胞遷入胚胎內(nèi)部，而要形成外胚層的細(xì)胞鋪展

13、在胚胎表面。原腸作用期，而要形成外胚層的細(xì)胞鋪展在胚胎表面。原腸作用期的胚胎叫的胚胎叫原腸胚原腸胚(gastrula)。l 通過原腸作用，通過原腸作用，胚胎首先建立起三個(gè)胚層，即外胚層、胚胎首先建立起三個(gè)胚層，即外胚層、中胚層和內(nèi)胚層中胚層和內(nèi)胚層；其次為重新占有新位置的；其次為重新占有新位置的胚胎細(xì)胞之胚胎細(xì)胞之間的相互作用間的相互作用奠定了基礎(chǔ)。因此，原腸作用是從尚未分奠定了基礎(chǔ)。因此，原腸作用是從尚未分化到分化為三個(gè)胚層和器官原基決定的關(guān)鍵時(shí)期。化到分化為三個(gè)胚層和器官原基決定的關(guān)鍵時(shí)期。l 動(dòng)物身體的主軸動(dòng)物身體的主軸（包括前后軸、背腹軸和左右軸）也（包括前后軸、背腹軸和左右軸）也會(huì)在

14、卵裂和原腸作用期間建立起來，胚胎各部分的細(xì)胞會(huì)在卵裂和原腸作用期間建立起來，胚胎各部分的細(xì)胞會(huì)獲得各自的發(fā)育潛能。會(huì)獲得各自的發(fā)育潛能。人類的原腸作用人類的原腸作用l 上胚層和下胚層的形成：上胚層和下胚層的形成：在原腸作用開始時(shí)，在原腸作用開始時(shí)，內(nèi)細(xì)胞團(tuán)分裂為兩層。內(nèi)細(xì)胞團(tuán)分裂為兩層。與囊與囊胚腔接觸的一層為下胚層，將用于形成胚腔接觸的一層為下胚層，將用于形成yolk sac；另一層為上胚層。上胚層另一層為上胚層。上胚層細(xì)胞間的縫隙將合并、擴(kuò)大成為羊膜腔，腔中的液體可防止胚胎脫水和保護(hù)細(xì)胞間的縫隙將合并、擴(kuò)大成為羊膜腔，腔中的液體可防止胚胎脫水和保護(hù)胚胎受振蕩。上胚層將發(fā)育為胚胎的本體。胚胎

15、受振蕩。上胚層將發(fā)育為胚胎的本體。原腸作用前的胚泡，示內(nèi)細(xì)胞團(tuán)和滋養(yǎng)層細(xì)胞。原腸作用前的胚泡，示內(nèi)細(xì)胞團(tuán)和滋養(yǎng)層細(xì)胞。下胚層細(xì)胞從內(nèi)細(xì)胞團(tuán)中分離出來形成卵黃囊，滋養(yǎng)層細(xì)胞分裂下胚層細(xì)胞從內(nèi)細(xì)胞團(tuán)中分離出來形成卵黃囊，滋養(yǎng)層細(xì)胞分裂形成形成細(xì)胞滋養(yǎng)層和合胞體滋養(yǎng)層細(xì)胞滋養(yǎng)層和合胞體滋養(yǎng)層；細(xì)胞滋養(yǎng)層形成絨毛，合胞體；細(xì)胞滋養(yǎng)層形成絨毛，合胞體滋養(yǎng)層融入子宮組織。滋養(yǎng)層融入子宮組織。上胚層分裂形成羊膜外胚層（包繞羊膜腔）和胚胎上胚上胚層分裂形成羊膜外胚層（包繞羊膜腔）和胚胎上胚層，哺乳類胚胎由胚胎上胚層形成。層，哺乳類胚胎由胚胎上胚層形成。胚外內(nèi)胚層形成卵黃囊胚外內(nèi)胚層形成卵黃囊人體胚胎三胚層的建

16、立及其命運(yùn)人體胚胎三胚層的建立及其命運(yùn)人類原腸作用過程中，羊膜結(jié)構(gòu)的形成和細(xì)胞的運(yùn)動(dòng)。人類原腸作用過程中，羊膜結(jié)構(gòu)的形成和細(xì)胞的運(yùn)動(dòng)。Note: the human epiblast is a flat disc. The mouse epiblast is cup-shaped-harder to visualize.40天妊娠后人類的天妊娠后人類的胚胎被羊膜包裹，胚胎被羊膜包裹，外面再被絨毛膜包外面再被絨毛膜包被。血管已深入到被。血管已深入到絨毛膜內(nèi)，絨毛膜絨毛膜內(nèi)，絨毛膜上的微絨毛最大限上的微絨毛最大限度地與母體血液接度地與母體血液接觸。觸。人類胚胎與母體間的物質(zhì)交流人類胚胎與母體間的物

17、質(zhì)交流人體胚胎細(xì)胞的分化路線人體胚胎細(xì)胞的分化路線Early post-implantation development of the mouse embryol Inner cell mass: primitive endoderm (extra-embryonic membrane) and primitive ectoderm or epiblast (embryo proper and some extra-embryonic components)l Polar trophectoderm: the ectoplacental cone and the placenta Mural

18、trophectoderm: trophoblast giant cellsEarly post-implantation development of the mouse embryol Egg cylinder: an internal cavity (proaminotic cavity) forms, U-shapedl Onset of gastrulation: the appearance of primitive streak小鼠胚胎上胚層細(xì)胞的程序性死亡導(dǎo)致囊胚腔的形成。小鼠胚胎上胚層細(xì)胞的程序性死亡導(dǎo)致囊胚腔的形成。Gastrulation in the mouse emb

19、ryol 6.5 d: beginning of gastrulation, the appearance of primitive streak; antero-posterior axisl 7.5 d: primitive streak elongates until the bottom of the cup, forming notochord (head process)Gastrulation and neurulation in the mouse embryol 7d: the node formation, anterior ectodermneurectoderm (br

20、ain and spinal cord)l The anterior part of the embryo grows in size and head fold appears, definitive endoderm replace visceral endoderm to form an outer layer on the ventral surface of the embryo. The notochord begins to form.Gastrulation and neurulation in the mouse embryol 8d: head is distinct, n

21、eural folds have formed, gut have closed, somites begins to form on either side of the notochord.l 10.5d: the complete of gastrulation and neurulation after turning.Tuning in the mouse embryol Turning: a developmental quirk peculiar to rodents: human embryos are surrounded by their extra-embryonic m

22、embranes from the beginning.l8.5-9.5d: the mouse embryo becomes entirely enclosed in the protective amnion and amniotic fluid. The visceral yolk sac, a major source of nutrition, surrounds the aminon, the umbilical cord connects to the placenta.胚軸形成胚軸形成 胚胎細(xì)胞形成不同組織、器官，構(gòu)成有序空間結(jié)構(gòu)胚胎細(xì)胞形成不同組織、器官，構(gòu)成有序空間結(jié)構(gòu)的過

23、程稱為的過程稱為圖式形成圖式形成（pattern formation）。）。 在動(dòng)物胚胎發(fā)育中，最初的圖式形成主要涉及胚軸在動(dòng)物胚胎發(fā)育中，最初的圖式形成主要涉及胚軸（embryonic axes）形成及其一系列相關(guān)的細(xì)胞）形成及其一系列相關(guān)的細(xì)胞分化過程。胚軸指胚胎的前后軸（分化過程。胚軸指胚胎的前后軸（anterior -posterior axis）和背）和背 腹軸（腹軸（dorsal -ventral axis）。）。胚軸的形成是在一系列基因的多層次、網(wǎng)胚軸的形成是在一系列基因的多層次、網(wǎng)絡(luò)性調(diào)控下完成的絡(luò)性調(diào)控下完成的。Body axes formation：小鼠胚胎發(fā)育的早期無法辨

24、認(rèn)體軸小鼠胚胎發(fā)育的早期無法辨認(rèn)體軸l The specification of the inner cell mass of a mouse embryo depends on the relative position of the cells with respect to the inside and outside of the embryos.l Transcription factors: Cdx2 (滋養(yǎng)層細(xì)胞的分滋養(yǎng)層細(xì)胞的分化化) and Oct/4 (內(nèi)細(xì)內(nèi)細(xì)胞團(tuán)的分化胞團(tuán)的分化)The axes of the early mouse embryol Blastocyst

25、 stage: 4d: inner cell mass is confined to embryonic region and this defines an embryonic-abembryonic axis (geometrically, not cell fate)5.5d: the antero-posterior axis visible, with the formation of primitive streak at the posterior end. The symmetry-breaking event is the specification of the anter

26、ior visceral endoderm (前端內(nèi)臟內(nèi)胚層前端內(nèi)臟內(nèi)胚層, AVE)l 5.5d: A small region of visceral endoderm at the distal-most end of the cup is specifies as AVE induced by Nodal signaling from the epiblast and begins to proliferate and extend to one side of epiblast.l The anterior fate is restricted to the distal regio

27、n by inhibitory signals from the extra-embryonic ectoderm to the proximal visceral endoderm; induces anterior ectodermThe symmetry-breaking event is the specification of the anterior visceral endoderm (前端內(nèi)臟內(nèi)胚層前端內(nèi)臟內(nèi)胚層, AVE)l 6.5d: primitive streak begins to form on the opposite side, marking the post

28、erior end of the axisRole of the AVE in establishing the anterior-posterior axis of the mouse embryoCylindrical SymmetryBilateral SymmetryAPCerberus (anti-Nodal)Dkk (anti-Wnt)Lefty (anti-Nodal)Otx2Anterior neural ectodermNodal,Cripto (co-receptorFor Nodal)Endo-mesoderminductionDay 5.25 Day 5.5 Day 6

29、.25orhypoblastEndo-mesoderm induction,Primitive streakwnt, brachyury, fgf expressedEpiblastectodermThe left-right asymmetryl While the vertebrate body is outwardly symmetric, most internal organs are in fact asymmetric with respect to the left and right sides, called left-right asymmetry, e.g., the

30、heart, the right lung has more lobes than the left.l 1/10,000 in humans, situs inversusl mutation in the iv gene causes 50% of mice have hearts that loop to the right.l Key proteins in establishing leftness: extracellelar signal protein Nodal and transcription factor Pitx2Determination of left-right

31、 asymmetry in the chickl left-right symmetry is broken at an early stage by the asymmetric activity of a proton-potassium pump (H+/K+-ATPase)l The release of Ca2+ from cells in the left side as part of the symmetry-breaking process.l Pitx2: leftness; Lefty (Nodal antagonist) provide midline barrier

32、to prevent Nodal crossing to the right-hand side; Activin inhibit Shh activityLeft-right asymmetry in the mouse embryol Cilia(纖毛纖毛)-directed flow generates left-right asymmetryl Directed leftward flow of extracellular fluid at the node at around the late head-fold stagel Leftward flow of fluid propa

33、gates the release of intracellular Ca2+ to upregulate Nodal expression on the left side胚層的來源和特化胚層的來源和特化 (specification)l Fate map: tell us which tissues the different regions of the embryo give rise tol The fate maps and the genes involved in germ-layer specification are more similar in all vertebra

34、te models than are in early axis specificationl 根據(jù)被標(biāo)記細(xì)胞的命運(yùn)，構(gòu)建兩棲類早期囊胚的命運(yùn)圖：根據(jù)被標(biāo)記細(xì)胞的命運(yùn)，構(gòu)建兩棲類早期囊胚的命運(yùn)圖：labeled by injection of high-molecular-weight molecules such as rhodamine (cannot pass through cell membranes), as rhodamine fluoresces red in UV light, so detected under a UV microscope. The fluorescen

35、t protein green fluorescent protein (GFP) is now widely used.胚層的來源和特化胚層的來源和特化 (specification)l Fate mapping of the early Xenopus embryo: C3 is labeled with fluorescein (green)- tailbud stage, the cells give rise to mesoderm cells胚層的來源和特化胚層的來源和特化 (specification)Fate map of a late Xenopus blastulal Ec

36、toderm: epidermis, nervous systeml Along the dorso-ventral axis the mesoderm: notochord, somites, heart, kidney and bloodl Endoderm overlying the mesoderm in the marginal zoneFate map of a mouse at the late gastrula stage l Node: exclusively notochordl The middle part of the streak: mainly lateral-p

37、late mesoderml The posterior part of the streak: tailbud, extra-embryonic mesoderm that forms the extra-embryonic membranes-the amnion, visceral yolk sac, allantois.不同脊椎動(dòng)物的不同脊椎動(dòng)物的 fate map 基于一個(gè)圖式的改變基于一個(gè)圖式的改變l Similarities: the future notochord mesoderm occupies a central dorsal position; the neural

38、ectoderm lies adjacent to the notochord, with the rest of the ectoderm anterior to it.l Differences: mainly to the yolkiness of the different eggs, which determines the patterns of cleavage and influences the shape of the early embryo. Endoderm overlying the mesoderm in the marginal zoneFate maps of

39、 vertebrate embryos at a late blastula or early gastrula早期脊椎動(dòng)物的胚胎細(xì)胞的命運(yùn)并未決定，是可以調(diào)整的早期脊椎動(dòng)物的胚胎細(xì)胞的命運(yùn)并未決定，是可以調(diào)整的l Fusion of mouse embryos give rise to a chimera (mice that are mosaics of cells with 2 different genetic constitutions-by fusing 2 embryos): 8-cell stage embryo of an unpigmented strain of mous

40、e is fused with a pigmented strain will give rise to a chimeric animall Grafting experiments: transplanting the cells or regions to a host embryo, if determined, they will develop according to their original position; if not yet determined, develop in line with the new positionl Early mouse embryos

41、can regulate to achieve the correct size: retains considerable capacity to regulate until late in gastrulation.l Inner cell mass remain pluripotent up to 4.5 days after fertilization-they can give rise to many cell types. Cells in ICM can be cultured to produce embryonic stem cells (ES cells)小鼠發(fā)育相關(guān)突

42、變的產(chǎn)生小鼠發(fā)育相關(guān)突變的產(chǎn)生l Studying the role of a particular gene in development, to study the effects of a mutation in that gene l Mice: transgenic techniques, overexpress or knock-out a given genel Introducing embryonic stem cells (ES cells) carrying the mutation into the blastocyst小鼠的中胚層誘導(dǎo)和模式建成發(fā)生在原條形成時(shí)期小鼠的

43、中胚層誘導(dǎo)和模式建成發(fā)生在原條形成時(shí)期l 6 days: the AVE induce anterior character in the underlying epiblast and early markers of the future primitive streak (PS) are restricted to the proximal epiblast l 6.5 days: BMP activates the expression of mesoderm markers and the posterior movement of cells expressing PS marke

44、rs results in PS formation小鼠的中胚層誘導(dǎo)和模式建成發(fā)生在原條形成時(shí)期小鼠的中胚層誘導(dǎo)和模式建成發(fā)生在原條形成時(shí)期 7 days: extra-embryonic mesoderm is produced from the posterior end of PS while the node forms at the anterior end, which will give rise to axial mesendoderm (form doral mesoderm and gut endoderm)小鼠的中胚層誘導(dǎo)和模式建成發(fā)生在原條形成時(shí)期小鼠的中胚層誘導(dǎo)和模式

45、建成發(fā)生在原條形成時(shí)期The molecular interactions within the streak at 6.5 daysl BMP activates the expression of mesoderm markers, Nodal and Wnt express in PS, establish the posterior end of the PS and for mesoderm formation.中胚層誘導(dǎo)和模式建成的信號(hào)蛋白中胚層誘導(dǎo)和模式建成的信號(hào)蛋白l Brachyury: earliest markers of mesoderm; Brachyury: a key transcription factor in mesoderm specification and patterning.中胚層誘導(dǎo)和模式建成的信號(hào)蛋白中胚層誘導(dǎo)和模式建成的信號(hào)蛋白Graded response to increasin