Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss.

Published

Journal Article

Here we studied the role of signaling through ErbB-family receptors in interactions between unmyelinated axons and non-myelinating Schwann cells in adult nerves. We generated transgenic mice that postnatally express a dominant-negative ErbB receptor in non-myelinating but not in myelinating Schwann cells. These mutant mice present a progressive peripheral neuropathy characterized by extensive Schwann cell proliferation and death, loss of unmyelinated axons and marked heat and cold pain insensitivity. At later stages, C-fiber sensory neurons die by apoptosis, a process that may result from reduced GDNF (glial cell line-derived neurotrophic factor) expression in the sciatic nerve. Neuregulin 1 (NRG1)-ErbB signaling mediates, therefore, reciprocal interactions between non-myelinating Schwann cells and unmyelinated sensory neuron axons that are critical for Schwann cell and C-fiber sensory neuron survival. This study provides new insights into ErbB signaling in adult Schwann cells, the contribution of non-myelinating Schwann cells in maintaining trophic support of sensory neurons, and the possible role of disrupted ErbB signaling in peripheral sensory neuropathies.

Full Text

Duke Authors

Cited Authors

  • Chen, S; Rio, C; Ji, R-R; Dikkes, P; Coggeshall, RE; Woolf, CJ; Corfas, G

Published Date

  • November 2003

Published In

Volume / Issue

  • 6 / 11

Start / End Page

  • 1186 - 1193

PubMed ID

  • 14555954

Pubmed Central ID

  • 14555954

International Standard Serial Number (ISSN)

  • 1097-6256

Digital Object Identifier (DOI)

  • 10.1038/nn1139

Language

  • eng

Conference Location

  • United States