Germ layer-specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm.
Germ layer-specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm.
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DOI：
10.7554/elife.36740
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发表时间：
2018-07-31
期刊：
影响因子：
7.7
通讯作者：
Martindale MQ
中科院分区：
文献类型：
--
作者：
Salinas-Saavedra M;Rock AQ;Martindale MQ
在三胚层动物中，PAR蛋白调节外胚层和内胚层上皮细胞的细胞极性和粘附连接。但是，在双胚层刺胞动物Nematostella vectensis的胚胎中，PAR蛋白在双功能胃胚层上皮的所有细胞中降解。使用免疫组织化学，CRISPR/Cas9诱变和mRNA过表达，我们描述了N. vectensis胚我们证明，aPKC/Par复合物调节β-连环蛋白在外胚层中的定位，通过稳定其在细胞粘附中的作用，并且内中胚层上皮细胞由不同于上覆外胚层的细胞粘附系统组织。我们还表明，异位表达的蜗牛基因，这是表达在中胚层衍生物中的bilaterians，是足以下调PAR-蛋白质和转位β-连环蛋白从交界处的细胞质中的外胚层细胞。这些数据为后生动物胚胎上皮结构和不同细胞行为的进化提供了分子基础。大多数动物-包括鸟类，鱼类和哺乳动物-都有对称的左右两侧，被称为两侧对称。在生命早期，这组动物的胚胎发育出三层不同的细胞：外胚层（外层），内胚层（内层）和中胚层（中层）。这些层然后继续形成动物的组织和器官。外胚层产生外部组织，如皮肤和神经系统;内胚层形成内部组织，如肠道;中胚层产生所有组织，如肌肉和血液。另一种较小的动物，称为刺胞动物，没有左右两侧。相反，它们具有“径向对称性”，这意味着它们有多个相同的部分排列在一个圆圈中。这些动物-包括珊瑚，水母和海葵-只发展两个不同的细胞层，相当于双层的外层和内层。刺胞动物在两侧对称动物之前进化，但它们的遗传物质同样复杂。那么，为什么这两个群体会进化成不同的细胞层呢？动物胚胎究竟是如何发育出这些不同的层的？为了解决这些问题，Salinas-Saavedra等人研究了海葵Nematostella vectensis的胚胎。被称为PAR蛋白的分子在控制细胞如何行为和相互附着（以及它们如何形成层）方面发挥着重要作用。因此，Salinas-Saavedra等人使用一种称为免疫组织化学的技术来观察细胞内部，检查了海葵胚胎两层细胞中的这些蛋白质。实验发现，在海葵中，与形成“肠道”的细胞相比，形成“皮肤”的细胞中的PAR蛋白质排列方式不同。换句话说，外层的细胞以与内层细胞不同的方式彼此附着，其中Par蛋白被“中胚层”基因降解。研究结果还表明，这些海葵拥有形成第三层中间细胞所需的一切。就像两侧对称动物一样，它们可能会将细胞移入或移出身体内部的表面，但它们并不自然地这样做。了解动物如何形成不同的细胞层对于研究进化和胚胎发育的科学家来说非常重要。但它也有更广泛的应用。例如，一些参与中胚层发育的细胞也参与形成肿瘤。这一领域的未来研究可以帮助科学家更多地了解癌症样细胞如何在动物中形成。
In triploblastic animals, Par-proteins regulate cell-polarity and adherens junctions of both ectodermal and endodermal epithelia. But, in embryos of the diploblastic cnidarian Nematostella vectensis, Par-proteins are degraded in all cells in the bifunctional gastrodermal epithelium. Using immunohistochemistry, CRISPR/Cas9 mutagenesis, and mRNA overexpression, we describe the functional association between Par-proteins, ß-catenin, and snail transcription factor genes in N. vectensis embryos. We demonstrate that the aPKC/Par complex regulates the localization of ß-catenin in the ectoderm by stabilizing its role in cell-adhesion, and that endomesodermal epithelial cells are organized by a different cell-adhesion system than overlying ectoderm. We also show that ectopic expression of snail genes, which are expressed in mesodermal derivatives in bilaterians, is sufficient to downregulate Par-proteins and translocate ß-catenin from the junctions to the cytoplasm in ectodermal cells. These data provide molecular insight into the evolution of epithelial structure and distinct cell behaviors in metazoan embryos. Most animals – including birds, fish and mammals – have symmetrical left and right sides, and are known as bilaterians. During early life, the embryos of animals in this group develop three distinct layers of cells: the ectoderm (outer layer), the endoderm (inner layer), and the mesoderm (middle layer). These layers then go on to form the animal’s tissues and organs. The ectoderm produces external tissues, such as the skin and the nervous system; the endoderm forms internal tissues, like the gut; and the mesoderm creates all tissues in between, like muscles and blood. Another, smaller group of animals, called cnidarians, do not have left and right sides. Instead, they have a ‘radial symmetry’, meaning they have multiple identical parts arranged in a circle. These animals – which include corals, jellyfish and sea anemones – only develop two distinct layers of cells, equivalent to the outer and inner layers of bilaterians. Cnidarians evolved before bilaterians, but their genetic material is equally complex. So why did these two groups evolve to have different layers of cells? And how exactly do animal embryos develop these distinct layers? To address these questions, Salinas-Saavedra et al. studied embryos of the sea anemone Nematostella vectensis. Molecules called Par-proteins play an important role in controlling how cells behave and attach to one another (and therefore how they form layers). So, using a technique called immunohistochemistry to look inside cells, Salinas-Saavedra et al. examined these proteins in the two layers of cells in sea anemone embryos. The experiments found that in the sea anemones, Par-proteins are arranged differently in cells that form the ‘skin’ compared to cells that form the ‘gut’. In other words, cells in the outer layer attach to one another in a different way than cells in the inner layer, where the Par-proteins are degraded by ‘mesodermal’ genes. The findings also show that these sea anemones have all they need to form a third middle layer of cells. Like bilaterians, they could potentially move cells in and out of sheets that line surfaces inside the body – but they do not naturally do this. Understanding how animals form different layers of cells is important for scientists studying evolution and the development of embryos. However, it also has wider applications. For instance, some cells involved in developing the mesoderm are also involved in forming tumors. Future research in this area could help scientists learn more about how cancer-like cells form in animals.