Title: 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.
Neuron (2012) 73, 729-742
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