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

Keith Z. Sabin, Peng Jiang, Micah D. Gearhart, Ron Stewart, Karen Echeverri

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Article number91
JournalCommunications biology
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2019

Bibliographical note

Funding Information:
This reseach was supported by a Regenerative Medicine Minnesota Grant and a NIH NCID R01 to KE. KZS has been supported by a NIH T32 GM113846 grant.

Publisher Copyright:
© 2019, The Author(s).

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