Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish.
Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish.
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DOI：
10.1038/s41467-017-00143-0
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发表时间：
2017-07-25
影响因子：
16.6
通讯作者：
Becker CG
中科院分区：
文献类型：
--
作者：
Wehner D;Tsarouchas TM;Michael A;Haase C;Weidinger G;Reimer MM;Becker T;Becker CG
脊髓损伤部位的抑制细胞外基质是哺乳动物轴突再生的主要障碍。相反，斑马鱼的细胞外基质允许大量轴突再生，从而恢复运动。然而，对促进生长的细胞外基质的调控和组成知之甚少。本研究表明，病变部位成纤维细胞样细胞中Wnt/β-catenin通路的活性对轴突的再生和功能恢复至关重要。Wnt/β-catenin信号传导诱导col12a1a/b的表达和XII胶原的沉积，这是轴突主动导航非神经损伤部位环境所必需的。过表达col12a1a可解除Wnt/β-catenin通路抑制的作用，并足以加速再生。我们证明，在具有高再生能力的脊椎动物中，Wnt/β-catenin信号控制病变部位细胞外基质的组成，并且我们确定胶原XII是轴突再生的启动子。这些发现表明Wnt/β-catenin通路和Collagen XII可能是非再生物种细胞外基质操作的靶点。斑马鱼脊髓损伤后，非神经细胞建立细胞外基质促进轴突再生，但其调控机制尚不清楚。在这里，作者表明病变部位成纤维细胞样细胞中的Wnt/β-catenin信号通过XII胶原沉积激活轴突再生。
The inhibitory extracellular matrix in a spinal lesion site is a major impediment to axonal regeneration in mammals. In contrast, the extracellular matrix in zebrafish allows substantial axon re-growth, leading to recovery of movement. However, little is known about regulation and composition of the growth-promoting extracellular matrix. Here we demonstrate that activity of the Wnt/β-catenin pathway in fibroblast-like cells in the lesion site is pivotal for axon re-growth and functional recovery. Wnt/β-catenin signaling induces expression of col12a1a/b and deposition of Collagen XII, which is necessary for axons to actively navigate the non-neural lesion site environment. Overexpression of col12a1a rescues the effects of Wnt/β-catenin pathway inhibition and is sufficient to accelerate regeneration. We demonstrate that in a vertebrate of high regenerative capacity, Wnt/β-catenin signaling controls the composition of the lesion site extracellular matrix and we identify Collagen XII as a promoter of axonal regeneration. These findings imply that the Wnt/β-catenin pathway and Collagen XII may be targets for extracellular matrix manipulations in non-regenerating species. Following spinal injury in zebrafish, non-neural cells establish an extracellular matrix to promote axon re-growth but how this is regulated is unclear. Here, the authors show that Wnt/β-catenin signaling in fibroblast-like cells at a lesion activates axon re-growth via deposition of Collagen XII.
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作者：
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通讯作者：
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