AP-1cFos/JunB/miR-200a regulate the pro-regenerative glial cell response during axolotl spinal cord regeneration.
Commun Biol, 2019;2:91.
Sabin KZ[1, 2], Jiang P[3], Gearhart MD[1], Stewart R[3], Echeverri K[4, 5]
Affiliations
PMID: 30854483DOI: 10.1038/s42003-019-0335-4
Impact factor: 6.548
Abstract
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-1cFos/JunB after injury, which promotes a pro-regenerative glial cell response. Injury induced upregulation of miR-200a in glial cells supresses c-Jun 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.
MeSH terms
Ambystoma mexicanum; Animals; Axons; Biomarkers; Fluorescent Antibody Technique; Gene Expression Regulation; Genes, jun; Glial Fibrillary Acidic Protein; Immunohistochemistry; Mice; MicroRNAs; Models, Biological; Neuroglia; Promoter Regions, Genetic; Protein Binding; Spinal Cord Regeneration; Transcription Factor AP-1
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