The lh3 Glycosyltransferase Directs Target-Selective Peripheral Nerve Regeneration.
The lh3 Glycosyltransferase Directs Target-Selective Peripheral Nerve Regeneration.
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DOI：
10.1016/j.neuron.2015.10.004
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发表时间：
2015-11-18
期刊：
影响因子：
16.2
通讯作者：
Granato M
中科院分区：
文献类型：
--
作者：
Isaacman-Beck J;Schneider V;Franzini-Armstrong C;Granato M
功能性PNS再生需要受损的轴突返回到其原始的突触靶点，但靶点选择性再生的机制仍然难以捉摸。使用活细胞成像在斑马鱼中，我们发现，再生的运动轴突表现出强烈的偏好，他们原来的肌肉领土，轴突探测正确和不正确的轨迹广泛之前，选择他们原来的path.We表明，这个过程需要糖基转移酶lh3和损伤后表达lh3在雪旺细胞是足够的恢复目标选择性再生。此外，我们表明，邻近横断部位的雪旺细胞表达lh3底物胶原4a5，并且在再生过程中胶原4a5使轴突不稳定，探测不适当的轨迹，以确保目标选择性再生，可能通过轴突排斥性狭缝1a。我们的研究结果表明，选择性ECM组件匹配再生轴突的亚群与它们的原始目标，并揭示了一个以前不受重视的机制，传递突触目标选择再生轴突在体内。
Functional PNS regeneration requires injured axons to return to their original synaptic targets, yet the mechanisms underlying target-selective regeneration have remained elusive. Using live-cell imaging in zebrafish we find that regenerating motor axons exhibit a strong preference for their original muscle territory, and that axons probe both correct and incorrect trajectories extensively before selecting their original path. We show that this process requires the glycosyltransferase lh3 and that post-injury expression of lh3 in Schwann cells is sufficient to restore target-selective regeneration. Moreover, we demonstrate that Schwann cells neighboring the transection site express the lh3 substrate collagen4a5 and that during regeneration collagen4a5 destabilizes axons probing inappropriate trajectories to ensure target-selective regeneration, possibly through the axonal repellant slit1a. Our results demonstrate that selective ECM components match subpopulations of regenerating axons with their original targets, and reveal a previously unappreciated mechanism that conveys synaptic target selection to regenerating axons in vivo.