FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Santiago, Chile.
Neural Dev. 2012 Jun 8;7:19. doi: 10.1186/1749-8104-7-19.
Understanding the cellular mechanisms regulating axon degeneration and regeneration is crucial for developing treatments for nerve injury and neurodegenerative disease. In neurons, axon degeneration is distinct from cell body death and often precedes or is associated with the onset of disease symptoms. In the peripheral nervous system of both vertebrates and invertebrates, after degeneration of detached fragments, axons can often regenerate to restore function. Many studies of axonal degeneration and regeneration have used in vitro approaches, but the influence of extrinsic cell types on these processes can only be fully addressed in live animals. Because of its simplicity and superficial location, the larval zebrafish posterior lateral line (pLL) nerve is an ideal model system for live studies of axon degeneration and regeneration.
We used laser axotomy and time-lapse imaging of pLL axons to characterize the roles of leukocytes, Schwann cells and target sensory hair cells in axon degeneration and regeneration in vivo. Immune cells were essential for efficient removal of axonal debris after axotomy. Schwann cells were required for proper fasciculation and pathfinding of regenerating axons to their target cells. Intact target hair cells were not themselves required for regeneration, but chemical ablation of neuromasts caused axons to transiently deviate from their normal paths.
Macrophages, Schwann cells, and target sensory organs are required for distinct aspects of pLL axon degeneration or regeneration in the zebrafish larva. Our work introduces a powerful vertebrate model for analyzing axonal degeneration and regeneration in the living animal and elucidating the role of extrinsic cell types in these processes.
理解调节轴突变性和再生的细胞机制对于开发神经损伤和神经退行性疾病的治疗方法至关重要。在神经元中，轴突变性与细胞体死亡不同，通常先于或与疾病症状的出现相关。在脊椎动物和无脊椎动物的周围神经系统中，在分离的片段变性后，轴突通常可以再生以恢复功能。许多关于轴突变性和再生的研究都使用了体外方法，但只有在活体动物中才能充分研究外源性细胞类型对这些过程的影响。由于其简单性和表面位置，幼虫斑马鱼后外侧线 (pLL) 神经是活体研究轴突变性和再生的理想模型系统。
我们使用激光轴突切断和 pLL 轴突的延时成像来表征白细胞、雪旺细胞和靶感觉毛细胞在体内轴突变性和再生中的作用。免疫细胞对于轴突切断后有效清除轴突碎片是必不可少的。雪旺细胞对于再生轴突的正确聚集和寻径到靶细胞是必需的。完整的靶感觉毛细胞本身并不需要再生，但感觉乳突的化学消融会导致轴突暂时偏离正常路径。
巨噬细胞、雪旺细胞和靶感觉器官对于斑马鱼幼虫 pLL 轴突变性或再生的不同方面是必需的。我们的工作引入了一种强大的脊椎动物模型，用于在活体动物中分析轴突变性和再生，并阐明外源性细胞类型在这些过程中的作用。
