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

被引:135
作者
Chen, SZ
Rio, C
Ji, RR
Dikkes, P
Coggeshall, RE
Woolf, CJ
Corfas, G
机构
[1] Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA
[2] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA
[3] Harvard Univ, Sch Med, Boston, MA 02129 USA
[4] Univ Texas, Med Branch, Dept Anat & Neurosci, Galveston, TX 77555 USA
关键词
D O I
10.1038/nn1139
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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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收藏
页码:1186 / 1193
页数:8
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