发育生物学

爪蟾背腹轴特化中Wnt 途径蛋白的作用
A-D: β-catenin 在 卵 裂 球 细胞核中的不同定位。 A ： 2 细 胞 期 β-catenin （orange）主要在背部表 面。 B ： 囊 胚 预 定 的 背 面 βcatenin染色显示核定位。 C： 核定位不在同一个胚 胎的腹面。 D：β-catenin的背部定位 持续到原肠期。 E：2细胞期的每个分裂球 都注射无活性的GSK-3引 起背轴形成。 F：Nieuwkoop Center通过 背部β-catenin的激活和腹 部TGF-β的激活的协调作 Figure Baidu Nhomakorabea0.23. The role of Wnt pathway proteins in dorsal-ventral axis specification. (A-D) 用产生的模型。 Differential translocation of
Figure 10.20. Organization of a secondary axis by dorsal blastopore lip tissue. (A) Dorsal lip tissue from an early gastrula is transplanted into another early gastrula in the region that normally becomes ventral epidermis. (B) The donor tissue invaginates and forms a second archenteron, and then a second embryonic axis. Both donor and host tissues are seen in the new neural tube, notochord, and somites. (C) Eventually, a second embryo forms that is joined to the host. (D) Structure of the dorsal blastopore lip region in an early Xenopus gastrula. (A-C after Hamburger 1988; D after Winklbauer and Schürfeld 1999 and Arendt and NüblerJung 1999.)
β-catenin into Xenopus blastomere nuclei. (A) Early 2-cell stage of Xenopus, showing β-catenin (orange) predominantly at the dorsal surface. (B) Presumptive dorsal side of a Xenopus blastula stained for β-catenin shows nuclear localization. (C) Such nuclear localization is not seen on the ventral side of the same embryo. (D) β-catenin dorsal localization persists through the gastrula stage. (E) Dorsal axis formation caused by the injection of both blastomeres of a 2-cell Xenopus embryo with dominant inactive GSK-3. Dorsal fate is actively suppressed by wild-type GSK-3. (F) Irenic model whereby the Nieuwkoop center (characterized by siamois gene expression and the ability to induce dorsal mesoderm) is created by the synergy of the activation of β-catenin dorsally and the activation of the TGF-β signal vegetally.
（一）中胚层的形成和分区
中胚层由其下方的植物极内胚层细胞诱导形成
实验：单独培养；组合培养 组合培养结果:预定外胚层细胞在植物极内胚层细胞释放因子 的诱导下分化为中胚层 中胚层诱导模式： 最背部的植物极细胞（Nieuwkoop中心）诱导背部的中胚层 （体节、脊索和组织者） 腹部和侧部的植物极细胞（靠近精子入卵一侧）诱导腹部（间 充质和血液）和中间（肌肉和肾脏）的中胚层形成
Figure 10.25. Summary of events hypothesized to bring about the induction of the organizer in the dorsal mesoderm.
组织者的形成
Cortical rotation causes the translocation of Disheveled protein to the dorsal side of the embryo. Dsh binds GSK-3, thereby allowing βcatenin to accumulate in the future dorsal portion of the embryo. During cleavage, β-catenin enters the nuclei and binds with Tcf3 to form a transcription factor that activates genes encoding proteins such as Siamois. Siamois and Lim-1, a transcription factor activated by the TGF-β pathway, function together to activate the goosecoid gene in the organizer. Goosecoid is a transcription factor that can activate genes whose proteins are responsible for the organizer‘s activities.
Nieuwkoop中心：囊胚最背部的植 物极细胞，含有背部化决定子，可 诱导组织者产生。
Summary of experiments by Nieuwkoop and by Nakamura and Takasaki (1970), showing mesodermal induction by vegetal endoderm. (A) Isolated animal cap cells become a mass of ciliated epidermis, isolated vegetal cells generate gutlike tissue, and isolated equatorial (marginal zone) cells become mesoderm. (B) If animal cap cells are combined with vegetal cap cells, many of the animal cells generate mesodermal tissue. (C) Model for mesoderm induction in Xenopus. A ventral signal (probably FGF2 or BMP4) is released throughout the vegetal region of the embryo. This induces the marginal cells to become mesoderm. On the dorsal side (away from the point of sperm entry), a signal is released by the vegetal cells of the Nieuwkoop center. This dorsal signal induces the formation of the Spemann organizer in the overlying marginal zone cells. The possible identity of this signal will be discussed later in this chapter. (C after De Robertis et
组织者：能够诱导外胚层形成神经系统，并能和 其他组织一起调整成为中轴器官的胚孔背唇部分。 二、初级胚胎诱导各阶段细胞间相互作用 初级胚胎诱导=神经诱导(neural induction)？ 初级诱导的三个阶段（爪蟾为例） （一）中胚层的形成和分区(卵裂期) （二）神经诱导--脊索诱导背部外胚层形成神经外胚 层并进一步分化 （三）中枢神经系统的区域化
胚胎诱导（embryonic induction)：诱导者和反应 者 诱导者：产生影响并引起另一种细胞或组织分化方 向变化的细胞或组织 反应组织：接受影响并改变分化方向的细胞或组织。 在动物胚胎发育过程中存在大量的和连续的诱导 作用-初级；次级；三级胚胎诱导
第一节 初级胚胎诱导
一、组织者的发现(1921-1924)
β-CATENIN和TGF-β蛋白相互作用 形成组织者和诱导中胚层产生
β-catenin在胚胎背部的定位
Model of the mechanism by which the Disheveled protein stabilizes β-catenin in the dorsal portion of the amphibian egg. (A) Disheveled (Dsh) associates with a particular set of proteins at the vegetal pole of the unfertilized egg. (B) Upon fertilization, these protein vesicles are translocated dorsally along subcortical microtubule tracks. (C) Disheveled is then released from its vesicles and is distributed in the future dorsal third of the 1-cell embryo. (D) Disheveled binds to and blocks the action of GSK-3, thereby preventing the degradation of β-catenin on the dorsal side of the embryo. (E) The nuclei of the blastomeres in the dorsal region of the embryo receive β-catenin, while the nuclei of those in the ventral region do not.
胚胎细胞相互作用 -胚胎诱导
在有机体发育过程中，一个区域的组织与另一个 区域的组织相互作用，引起后一种组织分化方向 上的变化过程称为胚胎诱导。 Spemann 1901年通过视杯诱导晶状体的形成发现 的。
切除将来形成晶状体的外胚层，移植其他部位外胚层到视 杯上，移植的外胚层发育为晶状体。 外胚层和视杯之间夹入其它组织，晶状体不能形成。 移植视杯至其它部位外胚层下，此处外胚层发育为晶状体。