Nature Neuroscience6, 1186 - 1193 (2003)
Published online: 12 October 2003; | doi:10.1038/nn1139
Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss
Suzhen Chen1, 5, Carlos Rio1, 4, 5, Ru-Rong Ji2, Pieter Dikkes1, Richard E Coggeshall3, Clifford J Woolf2
& Gabriel Corfas1
1
Division of Neuroscience, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
2
Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA.
3
Department of Anatomy and Neuroscience, University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
4
Present address: DIATER, Soledad 37, 2830 San Martin de la Vega, Madrid, Spain.
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.
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