Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, 55455, USA.
Marine Biological Laboratory, Eugene Bell Center for Regenerative Biology and Tissue Engineering, Woods Hole, 02543, MA, USA.
Commun Biol. 2019 Mar 6;2:91. doi: 10.1038/s42003-019-0335-4. eCollection 2019.
Salamanders have the remarkable ability to functionally regenerate after spinal cord transection. In response to injury, GFAP glial cells in the axolotl spinal cord proliferate and migrate to replace the missing neural tube and create a permissive environment for axon regeneration. Molecular pathways that regulate the pro-regenerative axolotl glial cell response are poorly understood. Here we show axolotl glial cells up-regulate AP-1 after injury, which promotes a pro-regenerative glial cell response. Injury induced upregulation of miR-200a in glial cells supresses expression in these cells. Inhibition of miR-200a during regeneration causes defects in axonal regrowth and transcriptomic analysis revealed that miR-200a inhibition leads to differential regulation of genes involved with reactive gliosis, the glial scar, extracellular matrix remodeling and axon guidance. This work identifies a unique role for miR-200a in inhibiting reactive gliosis in axolotl glial cells during spinal cord regeneration.
蝾螈具有在脊髓横断后进行功能再生的显著能力。在受到损伤后，美西螈脊髓中的 GFAP 神经胶质细胞增殖并迁移，以替代缺失的神经管，并为轴突再生创造一个许可的环境。调节促进再生的美西螈神经胶质细胞反应的分子途径知之甚少。在这里，我们发现蝾螈神经胶质细胞在受伤后会上调 AP-1，这促进了促再生的神经胶质细胞反应。损伤诱导神经胶质细胞中 miR-200a 的上调抑制了这些细胞中 的表达。在再生过程中抑制 miR-200a 会导致轴突再生缺陷，转录组分析显示 miR-200a 抑制导致与反应性神经胶质、神经胶质瘢痕、细胞外基质重塑和轴突导向相关的基因的差异调节。这项工作确定了 miR-200a 在抑制脊髓再生过程中蝾螈神经胶质细胞的反应性神经胶质中的独特作用。
