Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, Mexico.
Glia. 2020 Jul;68(7):1329-1346. doi: 10.1002/glia.23735. Epub 2019 Nov 7.
Cells of the oligodendrocyte (OLG) lineage engage in highly motile behaviors that are crucial for effective central nervous system (CNS) myelination. These behaviors include the guided migration of OLG progenitor cells (OPCs), the surveying of local environments by cellular processes extending from differentiating and pre-myelinating OLGs, and during the process of active myelin wrapping, the forward movement of the leading edge of the myelin sheath's inner tongue along the axon. Almost all of these motile behaviors are driven by actin cytoskeletal dynamics initiated within a lamellipodial structure that is located at the tip of cellular OLG/OPC processes and is structurally as well as functionally similar to the neuronal growth cone. Accordingly, coordinated stoichiometries of actin filament (F-actin) assembly and disassembly at these OLG/OPC growth cones have been implicated in directing process outgrowth and guidance, and the initiation of myelination. Nonetheless, the functional importance of the OLG/OPC growth cone still remains to be fully understood, and, as a unique aspect of actin cytoskeletal dynamics, F-actin depolymerization and disassembly start to predominate at the transition from myelination initiation to myelin wrapping. This review provides an overview of the current knowledge about OLG/OPC growth cones, and it proposes a model in which actin cytoskeletal dynamics in OLG/OPC growth cones are a main driver for morphological transformations and motile behaviors. Remarkably, these activities, at least at the later stages of OLG maturation, may be regulated independently from the transcriptional gene expression changes typically associated with CNS myelination.
少突胶质细胞(OLG)谱系的细胞会发生高度活跃的运动行为,这对中枢神经系统(CNS)髓鞘形成非常重要。这些行为包括少突胶质前体细胞(OPC)的定向迁移,分化和预髓鞘化的 OLG 细胞突起中细胞过程对局部环境的探测,以及在活跃的髓鞘包裹过程中,髓鞘内舌的前缘沿轴突向前移动。几乎所有这些活跃的运动行为都是由位于细胞 OLG/OPC 突起尖端的片状伪足结构内发起的肌动蛋白细胞骨架动力学驱动的,其结构和功能与神经元生长锥相似。因此,在这些 OLG/OPC 生长锥中,肌动蛋白丝(F-actin)组装和拆卸的协调化学计量学已被牵连到指导过程的延伸和引导以及髓鞘形成的启动。尽管如此,OLG/OPC 生长锥的功能重要性仍有待全面了解,并且作为肌动蛋白细胞骨架动力学的独特方面,F-actin 的解聚和拆卸在从髓鞘形成启动到髓鞘包裹的转变中开始占主导地位。这篇综述概述了当前关于 OLG/OPC 生长锥的知识,并提出了一个模型,即 OLG/OPC 生长锥中的肌动蛋白细胞骨架动力学是形态转化和活跃运动行为的主要驱动因素。值得注意的是,这些活动,至少在 OLG 成熟的后期阶段,可能与通常与 CNS 髓鞘形成相关的转录基因表达变化独立调节。