Gastruloids develop the three body axes in the absence of extraembryonic tissues and spatially localised signalling
Gastruloids develop the three body axes in the absence of extraembryonic tissues and spatially localised signalling
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原肠胚在没有胚胎外组织和空间局部信号传导的情况下发育出三个身体轴
DOI：
10.1101/104539
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
A. Martinez Arias
中科院分区：
文献类型：
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作者：
D. A. Turner;L. Alonso;M. Girgin;P. Baillie;C. Glodowski;P. Hayward;J. Collignon;C. Gustavsen;P. Serup;B. Steventon;M. Lutolf;A. Martinez Arias
在动物的发育过程中，三个体轴的建立是一个关键的步骤。在哺乳动物中，遗传学研究表明，来自胚外组织的精确部署的信号的组合在胚胎内定位前后轴（AP），并导致背腹（DV）和左右（LR）轴的出现。我们已经使用Gastruloids，胚胎类器官作为模型系统来理解这一过程，并发现它们能够发育AP，DV和LR轴，以及以镜像胚胎的方式进行轴向伸长。Gastruloids可以生长160小时，并从外胚层、中胚层和内胚层形成衍生物。我们专注于AP轴，并表明，在Gastruloids该轴是注册在T/Bra的表达在一个极点，对应于延长的尖端。我们发现T/Bra表达的定位依赖于Wnt/β-Catenin和Nodal/Smad 2，3信号传导的组合活性，并且BMP信号传导在该过程中是不稳定的。此外，AP轴规范发生在没有胚外组织和本地化的信号源。我们的实验表明，Nodal与Wnt/β-Catenin信号传导一起对于T/Bra的表达是必不可少的，但Wnt信号传导在轴的伸长中具有可分离的活性。这些结果使我们认为，在胚胎中，胚外组织的作用可能不是诱导轴，而是使胚胎打破其初始对称性并组织其轴的内在能力发生偏差。一句话总结确定数量的胚胎干细胞聚集体的培养导致自组织的胚胎样结构，在缺乏来自额外胚胎组织的局部信号传导的情况下，在Wnt和Nodal信号传导的自主影响下，发育身体的三个主轴。
Establishment of the three body axes is a critical step during animal development. In mammals, genetic studies have shown that a combination of precisely deployed signals from extraembryonic tissues position the anteroposterior axis (AP) within the embryo and lead to the emergence of the dorsoventral (DV) and left-right (LR) axes. We have used Gastruloids, embryonic organoids, as a model system to understand this process and find that they are able to develop AP, DV and LR axes as well as to undergo axial elongation in a manner that mirror embryos. The Gastruloids can be grown for 160 hours and form derivatives from ectoderm, mesoderm and endoderm. We focus on the AP axis and show that in the Gastruloids this axis is registered in the expression of T/Bra at one pole that corresponds to the tip of the elongation. We find that localisation of T/Bra expression depends on the combined activities of Wnt/β-Catenin and Nodal/Smad2,3 signalling, and that BMP signalling is dispensable for this process. Furthermore, AP axis specification occurs in the absence of both extraembryonic tissues and of localised sources of signalling. Our experiments show that Nodal, together with Wnt/β-Catenin signalling, is essential for the expression of T/Bra but that Wnt signalling has a separable activity in the elongation of the axis. The results lead us to suggest that, in the embryo, the role of the extraembryonic tissues might not be to induce the axes but to bias an intrinsic ability of the embryo to break its initial symmetry and organise its axes. One sentence summary Culture of aggregates of defined number of Embryonic Stem cells leads to self-organised embryo-like structures which, in the absence of localised signalling from extra embryonic tissues and under the autonomous influence of Wnt and Nodal signalling, develop the three main axes of the body.