NeuroD-null mice are deaf due to a severe loss of the inner ear sensory neurons during development.
NeuroD-null mice are deaf due to a severe loss of the inner ear sensory neurons during development.
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DOI：
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发表时间：
2001-02
期刊：
影响因子：
4.6
通讯作者：
W Y Kim-;Bernd Fritzsch;A. Serls;L. Bakel;E. Huang;L. Reichardt;D. Barth;J. E. Lee
中科院分区：
文献类型：
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作者：
W Y Kim-;Bernd Fritzsch;A. Serls;L. Bakel;E. Huang;L. Reichardt;D. Barth;J. E. Lee
神经系统遗传程序化发育的一个关键因素是大量神经元的死亡。因此，控制细胞存活的遗传机制对发育神经科学具有根本的重要性。我们报告说，内耳感觉神经元依赖于一个基本的螺旋-环-螺旋转录因子称为NeuroD的生存分化过程中。缺乏NeuroD蛋白的小鼠没有表现出听觉诱发电位，反映了严重的耳聋。DiI纤维染色、免疫组化和细胞死亡分析表明，耳聋是由于内耳感觉神经元在发育过程中存活失败所致。受影响的内耳感觉神经元不能表达神经营养因子受体TrkB和TrkC，这表明NeuroD支持神经元存活的能力可能是通过调节对神经营养因子的反应来直接介导的。
A key factor in the genetically programmed development of the nervous system is the death of massive numbers of neurons. Therefore, genetic mechanisms governing cell survival are of fundamental importance to developmental neuroscience. We report that inner ear sensory neurons are dependent on a basic helix-loop-helix transcription factor called NeuroD for survival during differentiation. Mice lacking NeuroD protein exhibit no auditory evoked potentials, reflecting a profound deafness. DiI fiber staining, immunostaining and cell death assays reveal that the deafness is due to the failure of inner ear sensory neuron survival during development. The affected inner ear sensory neurons fail to express neurotrophin receptors, TrkB and TrkC, suggesting that the ability of NeuroD to support neuronal survival may be directly mediated through regulation of responsiveness to the neurotrophins.