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

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...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Vol. 73; no. 4; p. 729
Main Authors: Napoli, Ilaria, Noon, Luke A, Ribeiro, Sara, Kerai, Ajay P, Parrinello, Simona, Rosenberg, Laura H, Collins, Melissa J, Harrisingh, Marie C, White, Ian J, Woodhoo, Ashwin, Lloyd, Alison C
Format: Journal Article
Language:English
Published: United States 23.02.2012
Subjects:
Animals
Animals, Newborn
Benzamides - pharmacology
Cell Movement - drug effects
Cyclin D1 - metabolism
Cytokines - metabolism
Diphenylamine - analogs & derivatives
Diphenylamine - pharmacology
Estrogen Antagonists - pharmacology
Gene Expression Regulation - drug effects
Gene Expression Regulation - genetics
Leukocytes - pathology
Male
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - genetics
MAP Kinase Signaling System - physiology
Mast Cells - pathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Confocal
Microscopy, Electron, Transmission
Microscopy, Immunoelectron
Motor Activity - drug effects
Motor Activity - genetics
Myelin Sheath - genetics
Myelin Sheath - metabolism
Nerve Regeneration - drug effects
Nerve Regeneration - genetics
Neutrophils - metabolism
Neutrophils - pathology
Peripheral Nerve Injuries - pathology
Peripheral Nerve Injuries - physiopathology
Proto-Oncogene Proteins c-raf - genetics
Proto-Oncogene Proteins c-raf - metabolism
Reaction Time - drug effects
Reaction Time - genetics
Receptor, Nerve Growth Factor - genetics
Receptor, Nerve Growth Factor - metabolism
Receptors, Estrogen - genetics
Recovery of Function - drug effects
Recovery of Function - genetics
Schwann Cells - physiology
Schwann Cells - ultrastructure
T-Lymphocytes - metabolism
T-Lymphocytes - pathology
Tamoxifen - pharmacology
Time Factors
ISSN:1097-4199, 1097-4199
Online Access:Get more information
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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.
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ISSN:1097-4199
1097-4199
DOI:10.1016/j.neuron.2011.11.031