细胞 EMT 的动态变化:胚胎发育活体成像的启示。
Cellular dynamics of EMT: lessons from live in vivo imaging of embryonic development.
机构信息
Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY, USA.
BioInspired Syracuse: Institute for Material and Living Systems, Syracuse, NY, USA.
出版信息
Cell Commun Signal. 2021 Jul 22;19(1):79. doi: 10.1186/s12964-021-00761-8.
Epithelial-mesenchymal transition (EMT) refers to a process in which epithelial cells lose apical-basal polarity and loosen cell-cell junctions to take on mesenchymal cell morphologies and invasive properties that facilitate migration through extracellular matrix. EMT-and the reverse mesenchymal-epithelial transition (MET)-are evolutionarily conserved processes that are used throughout embryonic development to drive tissue morphogenesis. During adult life, EMT is activated to close wounds after injury, but also can be used by cancers to promote metastasis. EMT is controlled by several mechanisms that depend on context. In response to cell-cell signaling and/or interactions with the local environment, cells undergoing EMT make rapid changes in kinase and adaptor proteins, adhesion and extracellular matrix molecules, and gene expression. Many of these changes modulate localization, activity, or expression of cytoskeletal proteins that mediate cell shape changes and cell motility. Since cellular changes during EMT are highly dynamic and context-dependent, it is ideal to analyze this process in situ in living organisms. Embryonic development of model organisms is amenable to live time-lapse microscopy, which provides an opportunity to watch EMT as it happens. Here, with a focus on functions of the actin cytoskeleton, I review recent examples of how live in vivo imaging of embryonic development has led to new insights into mechanisms of EMT. At the same time, I highlight specific developmental processes in model embryos-gastrulation in fly and mouse embryos, and neural crest cell development in zebrafish and frog embryos-that provide in vivo platforms for visualizing cellular dynamics during EMT. In addition, I introduce Kupffer's vesicle in the zebrafish embryo as a new model system to investigate EMT and MET. I discuss how these systems have provided insights into the dynamics of adherens junction remodeling, planar cell polarity signaling, cadherin functions, and cytoskeletal organization during EMT, which are not only important for understanding development, but also cancer progression. These findings shed light on mechanisms of actin cytoskeletal dynamics during EMT, and feature live in vivo imaging strategies that can be exploited in future work to identify new mechanisms of EMT and MET. Video Abstract.
上皮-间充质转化(EMT)是指上皮细胞失去顶端-基底极性并松开细胞-细胞连接,从而获得间充质细胞形态和侵袭特性,从而促进穿过细胞外基质的迁移。EMT 和相反的间充质-上皮转化(MET)是进化保守的过程,在胚胎发育过程中用于驱动组织形态发生。在成年期,EMT 在受伤后关闭伤口时被激活,但也可以被癌症利用来促进转移。EMT 受几种机制控制,这些机制取决于上下文。细胞在经历 EMT 时,会对细胞-细胞信号和/或与局部环境的相互作用做出快速反应,改变激酶和衔接蛋白、黏附和细胞外基质分子以及基因表达。其中许多变化调节细胞骨架蛋白的定位、活性或表达,这些蛋白介导细胞形状变化和细胞迁移。由于 EMT 期间的细胞变化高度动态且依赖于上下文,因此在活生物体中原位分析此过程是理想的。模式生物的胚胎发育适合进行活延时显微镜检查,这为观察 EMT 的发生提供了机会。在这里,我重点介绍肌动蛋白细胞骨架的功能,回顾了最近的一些例子,说明活体体内成像如何导致对 EMT 机制的新见解。同时,我突出了模型胚胎中的特定发育过程——果蝇和小鼠胚胎的原肠胚形成,以及斑马鱼和青蛙胚胎的神经嵴细胞发育,这些过程为观察 EMT 期间的细胞动力学提供了体内平台。此外,我还介绍了斑马鱼胚胎中的 Kupffer 泡作为研究 EMT 和 MET 的新模型系统。我讨论了这些系统如何深入了解 EMT 期间黏着连接重塑、平面细胞极性信号、钙粘蛋白功能和细胞骨架组织的动态,这些不仅对理解发育过程很重要,对癌症进展也很重要。这些发现揭示了 EMT 期间肌动蛋白细胞骨架动力学的机制,并展示了可用于未来工作的活体体内成像策略,以确定 EMT 和 MET 的新机制。视频摘要。