Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss
Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss
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DOI：
10.1038/nn1139
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发表时间：
2003-11-01
影响因子：
25
通讯作者：
Corfas, G
中科院分区：
文献类型：
--
作者：
Chen, SZ;Rio, C;Corfas, G
在这里，我们研究了 ErbB 家族受体信号传导在成人神经中无髓鞘轴突和非髓鞘雪旺细胞之间相互作用中的作用。我们培育出的转基因小鼠出生后在非髓鞘细胞中表达显性失活的 ErbB 受体，但在有髓鞘雪旺细胞中不表达。这些突变小鼠表现出进行性周围神经病变，其特征是广泛的雪旺细胞增殖和死亡、无髓鞘轴突的丧失以及明显的热和冷痛不敏感。在后期，C 纤维感觉神经元因细胞凋亡而死亡，这一过程可能是由于坐骨神经中 GDNF（胶质细胞源性神经营养因子）表达减少所致。因此，神经调节蛋白 1 (NRG1)-ErbB 信号传导介导非髓鞘化施万细胞和无髓鞘感觉神经元轴突之间的相互作用，这对于施万细胞和 C 纤维感觉神经元的存活至关重要。这项研究为成年雪旺细胞中的 ErbB 信号传导、非髓鞘雪旺细胞在维持感觉神经元营养支持中的贡献以及破坏的 ErbB 信号在周围感觉神经病中的可能作用提供了新的见解。
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.