A Central Role for the ERK-Signaling Pathway in Controlling Schwann Cell Plasticity and Peripheral Nerve Regeneration In Vivo
A Central Role for the ERK-Signaling Pathway in Controlling Schwann Cell Plasticity and Peripheral Nerve Regeneration In Vivo
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DOI：
10.1016/j.neuron.2011.11.031
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发表时间：
2012-02-23
期刊：
影响因子：
16.2
通讯作者：
Lloyd, Alison C.
中科院分区：
文献类型：
--
作者：
Napoli, Ilaria;Noon, Luke A.;Lloyd, Alison C.
周围神经受损后，会发生显著的清除和再生过程。损伤下游的轴突退化，而神经被重塑以引导轴突再生。雪旺细胞对这个再生过程很重要。“感知”受损的轴突，它们去分化为祖细胞样状态，在这种状态下它们有助于神经再生。在这里，我们证明了在有髓鞘的雪旺氏细胞中诱导的Raf-kinase转基因的激活足以通过在没有轴突损伤的情况下诱导严重的脱髓鞘来控制这种可塑性，其中脱髓鞘/共济失调的时期由Raf激活的持续时间确定。值得注意的是，Raf-kinase的激活也诱导了许多对神经修复重要的炎症反应，包括血神经屏障的破坏和炎性细胞的流入。这种可逆的体内模型确定了雪旺细胞中ERK信号传导在协调神经修复中的核心作用，并且是研究周围神经病变和癌症的强大系统。
Following damage to peripheral nerves, a remarkable process of clearance and regeneration takes place. Axons downstream of the injury degenerate, while the nerve is remodeled to direct axonal regrowth. Schwann cells are important for this regenerative process. "Sensing" damaged axons, they dedifferentiate to a progenitor-like state, in which they aid nerve regeneration. Here, we demonstrate that activation of an inducible Raf-kinase transgene in myelinated Schwann cells is sufficient to control this plasticity by inducing severe demyelination in the absence of axonal damage, with the period of demyelination/ataxia determined by the duration of Raf activation. Remarkably, activation of Raf-kinase also induces much of the inflammatory response important for nerve repair, including breakdown of the blood-nerve barrier and the influx of inflammatory cells. This reversible in vivo model identifies a central role for ERK signaling in Schwann cells in orchestrating nerve repair and is a powerful system for studying peripheral neuropathies and cancer.