Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1186-1193 |
| Number of pages | 8 |
| Journal | Nature Neuroscience |
| Volume | 6 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2003 |
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ASJC Scopus subject areas
- Neuroscience(all)
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Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss. / Chen, Suzhen; Rio, Carlos; Ji, Ru Rong; Dikkes, Pieter; Coggeshall, Richard E.; Woolf, Clifford J.; Corfas, Gabriel.
In: Nature Neuroscience, Vol. 6, No. 11, 11.2003, p. 1186-1193.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss
AU - Chen, Suzhen
AU - Rio, Carlos
AU - Ji, Ru Rong
AU - Dikkes, Pieter
AU - Coggeshall, Richard E.
AU - Woolf, Clifford J.
AU - Corfas, Gabriel
PY - 2003/11
Y1 - 2003/11
N2 - 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.
AB - 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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U2 - 10.1038/nn1139
DO - 10.1038/nn1139
M3 - Article
VL - 6
SP - 1186
EP - 1193
JO - Nature Neuroscience
JF - Nature Neuroscience
SN - 1097-6256
IS - 11
ER -