FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Santiago RM 7800003, Chile.
Int J Mol Sci. 2021 Mar 2;22(5):2484. doi: 10.3390/ijms22052484.
Following an injury, axons of both the central nervous system (CNS) and peripheral nervous system (PNS) degenerate through a coordinated and genetically conserved mechanism known as Wallerian degeneration (WD). Unlike central axons, severed peripheral axons have a higher capacity to regenerate and reinnervate their original targets, mainly because of the favorable environment that they inhabit and the presence of different cell types. Even though many aspects of regeneration in peripheral nerves have been studied, there is still a lack of understanding regarding the dynamics of axonal degeneration and regeneration, mostly due to the inherent limitations of most animal models. In this scenario, the use of zebrafish () larvae combined with time-lapse microscopy currently offers a unique experimental opportunity to monitor the dynamics of the regenerative process in the PNS in vivo. This review summarizes the current knowledge and advances made in understanding the dynamics of the regenerative process of PNS axons. By using different tools available in zebrafish such as electroablation of the posterior lateral line nerve (pLLn), and laser-mediated transection of motor and sensory axons followed by time-lapse microscopy, researchers are beginning to unravel the complexity of the spatiotemporal interactions among different cell types during the regenerative process. Thus, understanding the cellular and molecular mechanisms underlying the degeneration and regeneration of peripheral nerves will open new avenues in the treatment of acute nerve trauma or chronic conditions such as neurodegenerative diseases.
在受伤后,中枢神经系统 (CNS) 和周围神经系统 (PNS) 的轴突通过一种称为 Wallerian 变性 (WD) 的协调且遗传保守的机制退化。与中枢轴突不同,被切断的周围轴突具有更高的再生和重新支配其原始靶标的能力,主要是因为它们所处的有利环境和存在不同的细胞类型。尽管周围神经再生的许多方面已经得到研究,但对于轴突变性和再生的动态仍然缺乏了解,这主要是由于大多数动物模型的固有局限性。在这种情况下,使用斑马鱼()幼虫结合延时显微镜目前提供了一个独特的实验机会,可以在体内监测周围神经再生过程的动态。这篇综述总结了目前在理解周围神经轴突再生过程的动态方面的知识和进展。通过使用斑马鱼中可用的不同工具,例如后外侧线神经 (pLLn) 的电消融,以及通过延时显微镜对运动和感觉轴突进行激光介导的横切,研究人员开始揭示再生过程中不同细胞类型之间时空相互作用的复杂性。因此,了解周围神经变性和再生的细胞和分子机制将为急性神经创伤或神经退行性疾病等慢性疾病的治疗开辟新途径。