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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Veröffentlicht in:	Neuron (Cambridge, Mass.) Jg. 73; H. 4; S. 729
Hauptverfasser:	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
Sprache:	Englisch
Veröffentlicht:	United States 23.02.2012
Schlagworte:	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
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4199 1097-4199
DOI:	10.1016/j.neuron.2011.11.031