Science Direct paper for the Lloyd Group

A central role for the ERK-signalling pathway in controlling Schwann cell plasticity and peripheral nerve regeneration in vivo

Authors: Ilaria Napoli; Luke A. Noon; Sara Ribeiro; Simona Parrinello; Laura Rosenberg; Melissa Collins; Marie Harrisingh; Ian J. White; Ashwin Woodhoo; Kristjan R. Jessen; Rhona Mirsky and Alison C. Lloyd.

Summary

Following
damage to peripheral nerves, a remarkable process of clearance and
regeneration takes place. Axons downstream of the injury degenerate,
while the nerve is remodeled to direct axonal regrowth. Schwann cells
are important for this regenerative process. “Sensing” damaged axons,
they dedifferentiate to a progenitor-like state, in which they aid nerve
regeneration. Here, we demonstrate that activation of an inducible
Raf-kinase transgene in myelinated Schwann cells is sufficient to
control this plasticity by inducing severe demyelination in the absence
of axonal damage, with the period of demyelination/ataxia determined by
the duration of Raf activation. Remarkably, activation of Raf-kinase
also induces much of the inflammatory response important for nerve
repair, including breakdown of the blood-nerve barrier and the influx of
inflammatory cells. This reversible in vivo model identifies a central
role for ERK signaling in Schwann cells in orchestrating nerve repair
and is a powerful system for studying peripheral neuropathies and
cancer.