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AP-1cFos/JunB/miR-200a regulate the pro-regenerative glial cell response during axolotl spinal cord regeneration.


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.

SUBMITTER: Sabin KZ 

PROVIDER: S-EPMC6403268 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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AP-1<sup>cFos/JunB</sup>/miR-200a regulate the pro-regenerative glial cell response during axolotl spinal cord regeneration.

Sabin Keith Z KZ   Jiang Peng P   Gearhart Micah D MD   Stewart Ron R   Echeverri Karen K  

Communications biology 20190306


Salamanders have the remarkable ability to functionally regenerate after spinal cord transection. In response to injury, GFAP<sup>+</sup> 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<sup>cFos/JunB</sup> after injury, which promotes a  ...[more]

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