聽力的形成需要內耳毛細胞和蝸螺旋神經節(jié)之間形成高精度的突觸聯接,。這種高精度聯接可以保證內耳毛細胞所編碼的聲音信號以高保真的方式傳遞到下一級的聽力系統(tǒng),，最終形成我們對外部世界聲音信號的精確感知,。
在內耳聽覺系統(tǒng)的發(fā)育過程中，蝸螺旋神經節(jié)首先和內耳毛細胞的細胞胞體在空間上分離開來,，隨后蝸螺旋神經節(jié)的軸突再延伸到位于耳蝸的內耳毛細胞形成突觸聯接,。以前人們并不清楚這種空間上的分離和排列的機理。美國南加州大學的Shengzhi Wang, Li Zhang以及同事的最新研究發(fā)現,，Slit/Rob信號通路在這一過程中起到至關重要的作用,。他們發(fā)現,，軸突引導分子Slit2表達在耳蝸的上皮細胞而Slit2的受體,，Robo1/Robo2表達在蝸螺旋神經節(jié)上。在Slit2基因敲除小鼠內耳內,，部分蝸螺旋神經元分散到更加貼近內耳毛細胞的異常位置,，而這些異常蝸螺旋神經元的軸突沒有能夠正確地延伸到內耳毛細胞并形成突觸聯接。在Robo1/Robo2的基因敲除小鼠內,，這些零散分布在異常位置的蝸螺旋神經元同樣出現,。更加驚奇的發(fā)現是，蝸螺旋神經節(jié)作為一個整體更加貼近內耳毛細胞,。進一步的研究發(fā)現,，在這些變異的老鼠內耳中，蝸螺旋神經節(jié)和內耳毛細胞之間發(fā)育早期過程中的分離沒有出現異常,。這些蝸螺旋神經元是在晚期逐步脫離了正常的空間分布向內耳毛細胞貼近,。他們的研究成果表明,，Slit/Robo信號通路作用在蝸螺旋神經節(jié)上以保證它們的正常空間分布從而確保它們和內耳毛細胞之間形成精確的聯接,。這一研究成果將會對人類耳聾的疾病機理及治療提供重要的依據和啟發(fā),。 （生物谷Bioon.com）
生物谷推薦英文摘要：
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.
