Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells
Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells
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DOI：
10.1038/ncomms2445
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发表时间：
2013-02-01
影响因子：
16.6
通讯作者：
Malgrange, Brigitte
中科院分区：
文献类型：
--
作者：
Defourny, Jean;Poirrier, Anne-Lise;Malgrange, Brigitte
听觉需要耳蜗螺旋神经节神经元对感觉毛细胞的最佳传入神经支配。在这里，我们报告说，互补表达ephrin-A5在毛细胞和EphA 4受体螺旋神经节神经元群体控制的I型和II型传入纤维的内，外毛细胞，分别为目标。在缺乏肝配蛋白-A5或EphA 4正向信号传导的情况下，I型投射的子集异常地超过内毛细胞层并侵入外毛细胞区域。缺乏I型传入突触会损害从内毛细胞到听神经的神经传递。相比之下，I型投射的径向移位与突触前带的增加相一致，这可以增强外毛细胞的传入信号。Ephexin-1、cofilin和肌球蛋白轻链激酶在EphA 4下游起作用以诱导I型螺旋神经节神经元生长锥塌陷。我们的研究结果构成了Eph/ephrin介导的相互排斥机制，负责特定的分类在耳蜗中的听觉投射的第一个识别。
Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor among spiral ganglion neuron populations controls the targeting of type I and type II afferent fibres to inner and outer hair cells, respectively. In the absence of ephrin-A5 or EphA4 forward signalling, a subset of type I projections aberrantly overshoot the inner hair cell layer and invade the outer hair cell area. Lack of type I afferent synapses impairs neurotransmission from inner hair cells to the auditory nerve. By contrast, radial shift of type I projections coincides with a gain of presynaptic ribbons that could enhance the afferent signalling from outer hair cells. Ephexin-1, cofilin and myosin light chain kinase act downstream of EphA4 to induce type I spiral ganglion neuron growth cone collapse. Our findings constitute the first identification of an Eph/ephrin-mediated mutual repulsion mechanism responsible for specific sorting of auditory projections in the cochlea.