Establishment and Maintenance of Cell Polarity in the C. elegans Intestine
Establishment and Maintenance of Cell Polarity in the C. elegans Intestine
复制标题
DOI：
10.1007/978-3-319-14466-5_2
复制
发表时间：
2015-01-01
期刊：
影响因子：
--
通讯作者：
Hoffmann, Michael
中科院分区：
文献类型：
--
作者：
Bossinger, Olaf;Wiesenfahrt, Tobias;Hoffmann, Michael
线虫提供了一个强大的体内模型系统，在其中研究胚胎、幼虫和成体发育过程中上皮根部的极性。具体地说，对黏附连接的组装及其在组织形态发生和器官发生中的作用进行了非常详细的分析。在大多数线虫上皮细胞中，连接蛋白定位于复合顶端连接(CeAJ)，这是一个单一的电子密度结构，作为中枢，整合脊椎动物和果蝇中发现的不同类型连接(如紧密和粘连连接、桥粒、隔膜连接)的屏障/围栏和黏附功能。CeAJ的两个核心成分是HMP-1/alpha-catenin-HMP-2/beta-catenin-HMR-1/E-cadherin复合体(Ccc)和Dlg-1/Discs Large-AJM-1复合体(Dac)。顶端定位的PAR-3-PAR-6-PKC-3复合体和基侧定位的调控因子let-413/Scribble都参与了CeAJ的形成和成熟，而let-413还维持了胚胎中线虫上皮细胞的极化。从胚胎发育后期到幼虫发育，在维持上皮细胞极性方面，极化运输和质膜的脂质成分成为更多关注的焦点(例如，在肠道中，只有20个细胞组成的简单上皮管)。值得注意的是，大多数胚胎上皮极性关键分子的功能仍然对上皮管(如受精膜)的从头形成至关重要，但对于线虫胚胎后发育过程中维持其顶端基极性似乎是必不可少的。CeAJ促进了上皮细胞之间的强大黏附，从而为物理菌株提供了机械阻力。然而，与脊椎动物和果蝇不同的是，CCC不是一般细胞黏附所必需的。在线虫胚胎肠道中，至少有两个黏附系统，包括HMR-1/E-cadherin和SAX-7/L1CAM，相关的连接蛋白(例如DAC)和细胞骨架组织者(例如ERM-1/Ezrin-Radisin-moesin，IFO-1，也称为TTM-4)，冗余地调节肠道CeAJ的黏附。在本章中，我们将首先关注线虫肠道发育的一般方面，包括规范、细胞增殖和基本解剖学。然后我们讨论了根尖管膜结构域(ALMD)的建立、CeAJ的组装以及管腔和刷状边界的形成。接下来，我们看看黏附系统和细胞骨架组织者，它们运行在CeAJ和心尖下细胞质中，使管腔具有高度的机械弹性，并确保肠管的完整性。最后，我们考虑了驱动ALMD扩张的机制，并在线虫的生命周期中维持肠道的顶端基极。
C. elegans provides a powerful in vivo model system in which to study epithelial apicobasal polarity during embryonic, larval, and adult development. Specifically, the assembly of adherens junctions and their role in tissue morphogenesis and organogenesis have been analyzed in great detail. In most C. elegans epithelia, junctional proteins localize to the multiplex apical junction (CeAJ), a single electron-dense structure that acts as a hub to integrate the barrier/fence and adhesive functions of different types of junctions found in vertebrates and Drosophila (e.g., tight and adherens junctions, desmosomes, septate junction).Two core components of the CeAJ are the HMP-1/alpha-catenin-HMP-2/beta-catenin-HMR-1/E-cadherin complex (CCC) and the DLG-1/Discs large-AJM-1 complex (DAC). The apically localized PAR-3-PAR-6-PKC-3 complex and the basolaterally localized regulator LET-413/Scribble both mediate the formation and maturation of the CeAJ, whereas LET-413 additionally maintains the polarization of C. elegans epithelia in the embryo. Starting in late embryogenesis and advancing in larval development, polarized trafficking and the lipid composition of the plasma membrane come more into focus with regard to the maintenance of epithelial cell polarity (e.g., in the intestine, a simple epithelial tube made of only 20 cells). Remarkably, the function of most embryonic epithelial polarity key players is still crucial for the de novo formation of epithelial tubes (e.g., the spermatheca) but seems dispensable for the maintenance of their apicobasal polarity during C. elegans postembryonic development.The CeAJ promotes robust adhesion between epithelial cells and thus provides mechanical resistance for physical strains. However, in contrast to vertebrates and Drosophila, the CCC is not essential for general cell adhesion. In the C. elegans embryonic intestine, at least two adhesion systems, including HMR-1/E-cadherin and SAX-7/L1CAM, associated linker proteins (e.g., the DAC), and cytoskeletal organizers (e.g., ERM-1/ezrin-radixin-moesin, IFO-1, also referred to as TTM-4), act redundantly to mediate adhesion at the intestinal CeAJ.In this chapter, we will first focus on the general aspects of intestinal development in C. elegans including specification, cell proliferation, and basic anatomy. We then discuss the establishment of the apicoluminal membrane domain (ALMD), the assembly of the CeAJ, and the formation of the lumen and the brush border. Next, we look at adhesion systems and cytoskeletal organizers that operate at the CeAJ and in the subapical cytoplasm to equip the lumen with a high degree of mechanical resilience and to ensure the integrity of the intestinal tube. Finally, we consider mechanisms that drive the expansion of the ALMD and maintain the apicobasal polarity of the intestine during the C. elegans' life cycle.