原腸胚形成

title: 体内(羊膜上).
title: 总览.
content: 在羊膜(爬行类、鸟类、哺乳动物)上,原肠胚形成与原肠腔(archenteron)上出现的一个开口,胚孔的出现有密切关系。注意胚孔并不是囊胚阶段上囊胚腔上的开口,而是一个新的开口。胚孔能推动囊胚表面的细胞聚合在一起。在羊膜上,原肠胚形成可以分为以下几个大步骤:一,胚胎变为不对称;二,原条形成;三,原条表皮细胞发生上皮-间充质转换。同时,原条区域细胞发生内移,形成胚层。  原口动物(protostome)和后口动物(deuterostome)口肛发生的差异在于,原口动物口的发生先于肛门,胚孔会发育为口。而后口动物口的发生后于肛门,胚孔会发育为肛门。它们的英文名也正是据此而来:原口动物(protostome)的英文名来自两个希腊语单词:「πρώτος + στόμα」,意思分别为「先」和「口」。后口动物(deuterostom)的英文名同样来自两个希腊单词:「δεύτερος + στόμα」,意思分别是「第二」(次)和「口」。
title: 对称性的失去.
content: 在原肠胚形成的准备阶段,胚胎会形成远近轴(proximal-distal axis)以及前后轴(anterior-posterior axis),不对称性也随这两个轴的发生而出现。胚胎的卵圆筒形成标志着远近轴的形成:近端的胚胎外组织会形成胎盘样组织,而远端则是上胚层。骨塑型蛋白(BMP)、成纤维细胞生长因子(FGF)、Nodal、Wnt等信号分子介导的信号转导途径参与了这一过程。内脏内胚层包围表皮。远端内脏内胚层(DVE)会迁移到胚胎的前部,形成前内脏内胚层(AVE),打破前后对称性。上述过程受Nodal信号通路的调控。
title: 原条的产生.
content: 原条在原肠胚形成的初始阶段产生。原条位于后侧胚胎外组织以及表皮之间的连结处以及内移发生的区域。原条的形成与科氏镰区域的细胞中的NODAL信号通路以及由胚胎外组织激活的BMP4信号通路有很大关系。Cer1和Lefty1通过拮抗Nodal信号通路,能将原条形成限制在特定区域。原条区域(在形成后)会继续往远端生长。  During the early stages of development, the primitive streak is the structure that will establish bilateral symmetry, determine the site of gastrulation and initiate germ layer formation. To form the streak, reptiles, birds and mammals arrange mesenchymal cells along the prospective midline, establishing the first embryonic axis, as well as the place where cells will ingress and migrate during the process of gastrulation and germ layer formation. The primitive streak extends through this midline and creates the antero-posterior body axis, becoming the first symmetry-breaking event in the embryo, and marks the beginning of gastrulation. This process involves the ingression of mesoderm and endoderm progenitors and their migration to their ultimate position, where they will differentiate into the three germ layers. The localization of the cell adhesion and signaling molecule beta-catenin is critical to the proper formation of the organizer region that is responsible for initiating gastrulation.
title: 上皮-间充质转换与内移.
content: In order for the cells to move from the epithelium of the epiblast through the primitive streak to form a new layer, the cells must undergo an epithelial to mesenchymal transition (EMT) to lose their epithelial characteristics, such as cell-cell adhesion. FGF signaling is necessary for proper EMT. FGFR1 is needed for the up regulation of SNAI1, which down regulates E-cadherin, causing a loss of cell adhesion. Following the EMT, the cells ingress through the primitive streak and spread out to form a new layer of cells or join existing layers. FGF8 is implicated in the process of this dispersal from the primitive streak.
title: 体外原肠胚形成.
content: 许多科学家都在尝试通过体外实验的方法与胚胎实验进行对比对照,以更加深入的研究原肠胚形成的过程。通常,研究人员会使用2D(传统)或3D(培养拟原肠胚(Gastruloid)的细胞培养方法培养胚胎干细胞(ESC)或人工诱导性多能干细胞(iPSC)。基于多种组织培养方法的体外培养方法相比体内实验的方法有成本低、符合3R原则、能以空间和时间特异性的方式准确地使用激动剂/拮抗剂等优势(在体内的原肠胚发生时期就很难做到第三点)。不过,体外实验多少会和体内实验存在差异,因而与体内的胚胎发育进行对比是必要的。 To illustrate this, the guided differentiation of mouse ESCs has resulted in generating primitive streak-like cells that display many of the characteristics of epiblast cells that traverse through the primitive streak (e.g. transient brachyury up regulation and the cellular changes associated with an epithelial to mesenchymal transition), and human ESCs cultured on micro patterns, treated with BMP4, can generate spatial differentiation pattern similar to the arrangement of the germ layers in the human embryo. Finally, using 3D embryoid body- and organoid-based techniques, small aggregates of mouse ESCs (Embryonic Organoids, or Gastruloids) are able to show a number of processes of early mammalian embryo development such as symmetry-breaking, polarisation of gene expression, gastrulation-like movements, axial elongation and the generation of all three embryonic axes (anteroposterior, dorsoventral and left-right axes).

Summary: 原肠胚形成(Gastrulation)是大部分动物胚胎发育中都会经历的一个阶段。在本阶段中,只有一层细胞的囊胚会发生重组,形成一个含有三个胚层(即外胚层(ectoderm)、中胚层(mesoderm)、内胚层(endoderm))细胞的原肠胚(gastrula)。

Gastrulation: Gastrulation (von griech. "gaster" „Bauch eines Gefäßes“) bezeichnet eine Phase der Embryogenese der vielzelligen Tiere, zu denen auch der Mensch gehört. Dabei stülpt sich die Blastula ein und es kommt zur Ausbildung der Keimblätter. Vorausgegangen ist die Ausbildung des Blasenkeimes, die sogenannte Blastulation. Dem britischen Entwicklungsbiologen Lewis Wolpert wird folgendes Zitat über die Gastrulation zugeschrieben: