c-Jun Reprograms Schwann Cells of Injured Nerves to Generate a Repair Cell Essential for Regeneration

TLDR

The radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. Activation of the transcription factor c‑Jun in Schwann cells globally regulates the Wallerian degeneration response, driving trophic factor expression, adhesion, regeneration track formation, and myelin clearance, and its absence produces dysfunctional repair cells, impaired functional recovery, and neuronal death. A single glial transcription factor, c‑Jun, is essential for nerve repair by controlling transdifferentiation of myelin and Remak Schwann cells into dedicated repair cells.

Abstract

SummaryThe radical response of peripheral nerves to injury (Wallerian degeneration) is the cornerstone of nerve repair. We show that activation of the transcription factor c-Jun in Schwann cells is a global regulator of Wallerian degeneration. c-Jun governs major aspects of the injury response, determines the expression of trophic factors, adhesion molecules, the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves. A key function of c-Jun is the activation of a repair program in Schwann cells and the creation of a cell specialized to support regeneration. We show that absence of c-Jun results in the formation of a dysfunctional repair cell, striking failure of functional recovery, and neuronal death. We conclude that a single glial transcription factor is essential for restoration of damaged nerves, acting to control the transdifferentiation of myelin and Remak Schwann cells to dedicated repair cells in damaged tissue.Highlights•Schwann cell c-Jun is a master regulator of the PNS injury response•c-Jun activates a defined repair program in Schwann cells of damaged nerves•c-Jun controls transdifferentiation of differentiated Schwann cells to repair cells•Schwann cell c-Jun is essential for neuronal survival and functional recovery