Target-selective vertebrate motor axon regeneration depends on interaction with glial cells at a peripheral nerve plexus.
Target-selective vertebrate motor axon regeneration depends on interaction with glial cells at a peripheral nerve plexus.
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DOI：
10.1371/journal.pbio.3002223
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发表时间：
2023-08
期刊：
影响因子：
9.8
通讯作者：
Granato, Michael
中科院分区：
文献类型：
--
作者：
Walker, Lauren J.;Guevara, Camilo;Kawakami, Koichi;Granato, Michael
周围神经损伤后功能恢复的关键步骤是再生轴突与损伤前靶点连接。重建损伤前的目标特异性对于四肢支配轴突来说尤其具有挑战性，因为它们遇到丛，这是一个周围神经聚集的网络，来自不同神经的轴突混合在一起，然后重新分类成目标特异性束。在这里，我们检查位于斑马鱼胸鳍底部的神经丛的这个过程，相当于四足动物的前肢。通过活细胞成像和稀疏轴突标记，我们发现来自3个神经的再生运动轴突合并到神经丛中。在那里，它们混合并分类成不同的分支，然后以高保真度导航到原来的肌肉区域，从而恢复功能。我们证明，这种再生过程包括选择性回缩错靶轴突，提示主动纠正机制。此外，我们发现雪旺细胞在神经丛中富集并与轴突相关联，并且在再生过程中雪旺细胞的消融会导致严重的轴突错靶。我们的数据首次提供了脊椎动物运动轴突在神经丛中导航的实时记录，并揭示了雪旺细胞在再生过程中促进神经丛轴突分选的作用。周围神经损伤后功能恢复的关键步骤是再生轴突与损伤前靶点连接。本研究表明，在斑马鱼胸鳍幼鱼运动轴突再生过程中，运动轴突在雪旺细胞的辅助下，对其原有的肌纤维靶点进行特异性的再神经支配。
A critical step for functional recovery from peripheral nerve injury is for regenerating axons to connect with their pre-injury targets. Reestablishing pre-injury target specificity is particularly challenging for limb-innervating axons as they encounter a plexus, a network where peripheral nerves converge, axons from different nerves intermingle, and then re-sort into target-specific bundles. Here, we examine this process at a plexus located at the base of the zebrafish pectoral fin, equivalent to tetrapod forelimbs. Using live cell imaging and sparse axon labeling, we find that regenerating motor axons from 3 nerves coalesce into the plexus. There, they intermingle and sort into distinct branches, and then navigate to their original muscle domains with high fidelity that restores functionality. We demonstrate that this regeneration process includes selective retraction of mistargeted axons, suggesting active correction mechanisms. Moreover, we find that Schwann cells are enriched and associate with axons at the plexus, and that Schwann cell ablation during regeneration causes profound axonal mistargeting. Our data provide the first real-time account of regenerating vertebrate motor axons navigating a nerve plexus and reveal a previously unappreciated role for Schwann cells to promote axon sorting at a plexus during regeneration. A critical step for functional recovery from peripheral nerve injury is for regenerating axons to connect with their pre-injury targets. This study shows that during motor axon regeneration in the larval zebrafish pectoral fin, motor axons are aided by Schwann cells to reinnervate their original muscle fiber targets with specificity.
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