Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss.
Journal Article (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.
- Chen, S; Rio, C; Ji, R-R; Dikkes, P; Coggeshall, RE; Woolf, CJ; Corfas, G
- November 2003
Volume / Issue
- 6 / 11
Start / End Page
- 1186 - 1193
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)
- United States