听力的形成需要内耳毛细胞和蜗螺旋神经节之间形成高精度的突触联接。这种高精度联接可以保证内耳毛细胞所编码的声音信号以高保真的方式传递到下一级的听力系统，最终形成我们对外部世界声音信号的精确感知。
在内耳听觉系统的发育过程中，蜗螺旋神经节首先和内耳毛细胞的细胞胞体在空间上分离开来，随后蜗螺旋神经节的轴突再延伸到位于耳蜗的内耳毛细胞形成突触联接。以前人们并不清楚这种空间上的分离和排列的机理。美国南加州大学的Shengzhi Wang, Li Zhang以及同事的最新研究发现，Slit/Rob信号通路在这一过程中起到至关重要的作用。他们发现，轴突引导分子Slit2表达在耳蜗的上皮细胞而Slit2的受体，Robo1/Robo2表达在蜗螺旋神经节上。在Slit2基因敲除小鼠内耳内，部分蜗螺旋神经元分散到更加贴近内耳毛细胞的异常位置，而这些异常蜗螺旋神经元的轴突没有能够正确地延伸到内耳毛细胞并形成突触联接。在Robo1/Robo2的基因敲除小鼠内，这些零散分布在异常位置的蜗螺旋神经元同样出现。更加惊奇的发现是，蜗螺旋神经节作为一个整体更加贴近内耳毛细胞。进一步的研究发现，在这些变异的老鼠内耳中，蜗螺旋神经节和内耳毛细胞之间发育早期过程中的分离没有出现异常。这些蜗螺旋神经元是在晚期逐步脱离了正常的空间分布向内耳毛细胞贴近。他们的研究成果表明，Slit/Robo信号通路作用在蜗螺旋神经节上以保证它们的正常空间分布从而确保它们和内耳毛细胞之间形成精确的联接。这一研究成果将会对人类耳聋的疾病机理及治疗提供重要的依据和启发。 （生物谷Bioon.com）
生物谷推荐英文摘要：
The Journal of Neuroscience, doi:10.1523/JNEUROSCI.5736-12.2013
Slit/Robo Signaling Mediates Spatial Positioning of Spiral Ganglion Neurons during Development of Cochlear Innervation
Sheng-zhi Wang, Leena A. Ibrahim, Young J. Kim, Daniel A. Gibson, Haiwen C. Leung, Wei Yuan, Ke K. Zhang, Huizhong W. Tao, Le Ma, and Li I. Zhang
During the development of periphery auditory circuits, spiral ganglion neurons (SGNs) extend their neurites to innervate cochlear hair cells (HCs) with their soma aggregated into a cluster spatially segregated from the cochlear sensory epithelium. The molecular mechanisms underlying this spatial patterning remain unclear. In this study, in situ hybridization in the mouse cochlea suggests that Slit2 and its receptor, Robo1/2, exhibit apparently complementary expression patterns in the spiral ganglion and its nearby region, the spiral limbus. In Slit2 and Robo1/2 mutants, the spatial restriction of SGNs was disrupted. Mispositioned SGNs were found to scatter in the space between the cochlear epithelium and the main body of spiral ganglion, and the neurites of mispositioned SGNs were misrouted and failed to innervate HCs. Furthermore, in Robo1/2 mutants, SGNs were displaced toward the cochlear epithelium as an entirety. Examination of different embryonic stages in the mutants revealed that the mispositioning of SGNs was due to a progressive displacement to ectopic locations after their initial normal settlement at an earlier stage. Our results suggest that Slit/Robo signaling imposes a restriction force on SGNs to ensure their precise positioning for correct SGN-HC innervations.
