Preston Marnie A, Macklin Wendy B
Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado.
Glia. 2015 Feb;63(2):177-93. doi: 10.1002/glia.22755. Epub 2014 Sep 27.
Myelin plays a critical role in proper neuronal function by providing trophic and metabolic support to axons and facilitating energy-efficient saltatory conduction. Myelination is influenced by numerous molecules including growth factors, hormones, transmembrane receptors and extracellular molecules, which activate signaling cascades that drive cellular maturation. Key signaling molecules and downstream signaling cascades controlling myelination have been identified in cell culture systems. However, in vitro systems are not able to faithfully replicate the complex in vivo signaling environment that occurs during development or following injury. Currently, it remains time-consuming and expensive to investigate myelination in vivo in rodents, the most widely used model for studying mammalian myelination. As such, there is a need for alternative in vivo myelination models, particularly ones that can test molecular mechanisms without removing oligodendrocyte lineage cells from their native signaling environment or disrupting intercellular interactions with other cell types present during myelination. Here, we review the ever-increasing role of zebrafish in studies uncovering novel mechanisms controlling vertebrate myelination. These innovative studies range from observations of the behavior of single cells during in vivo myelination as well as mutagenesis- and pharmacology-based screens in whole animals. Additionally, we discuss recent efforts to develop novel models of demyelination and oligodendrocyte cell death in adult zebrafish for the study of cellular behavior in real time during repair and regeneration of damaged nervous systems.
髓磷脂通过为轴突提供营养和代谢支持并促进节能的跳跃式传导，在神经元的正常功能中发挥关键作用。髓鞘形成受多种分子影响，包括生长因子、激素、跨膜受体和细胞外分子，这些分子激活驱动细胞成熟的信号级联反应。在细胞培养系统中已鉴定出控制髓鞘形成的关键信号分子和下游信号级联反应。然而，体外系统无法如实地复制发育过程中或损伤后体内发生的复杂信号环境。目前，在啮齿动物体内研究髓鞘形成仍然耗时且昂贵，啮齿动物是研究哺乳动物髓鞘形成最广泛使用的模型。因此，需要替代的体内髓鞘形成模型，特别是那些能够在不将少突胶质细胞谱系细胞从其天然信号环境中移除或破坏与髓鞘形成过程中存在的其他细胞类型的细胞间相互作用的情况下测试分子机制的模型。在这里，我们综述了斑马鱼在揭示控制脊椎动物髓鞘形成新机制的研究中日益重要的作用。这些创新性研究涵盖了从体内髓鞘形成过程中单个细胞行为的观察到基于全动物诱变和药理学的筛选。此外，我们讨论了最近为在成年斑马鱼中开发脱髓鞘和少突胶质细胞死亡的新模型所做的努力，以便实时研究受损神经系统修复和再生过程中的细胞行为。
