Colantonio Jessica R, Vermot Julien, Wu David, Langenbacher Adam D, Fraser Scott, Chen Jau-Nian, Hill Kent L
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
Nature. 2009 Jan 8;457(7226):205-9. doi: 10.1038/nature07520. Epub 2008 Nov 30.
In teleosts, proper balance and hearing depend on mechanical sensors in the inner ear. These sensors include actin-based microvilli and microtubule-based cilia that extend from the surface of sensory hair cells and attach to biomineralized 'ear stones' (or otoliths). Otolith number, size and placement are under strict developmental control, but the mechanisms that ensure otolith assembly atop specific cells of the sensory epithelium are unclear. Here we demonstrate that cilia motility is required for normal otolith assembly and localization. Using in vivo video microscopy, we show that motile tether cilia at opposite poles of the otic vesicle create fluid vortices that attract otolith precursor particles, thereby biasing an otherwise random distribution to direct localized otolith seeding on tether cilia. Independent knockdown of subunits for the dynein regulatory complex and outer-arm dynein disrupt cilia motility, leading to defective otolith biogenesis. These results demonstrate a requirement for the dynein regulatory complex in vertebrates and show that cilia-driven flow is a key epigenetic factor in controlling otolith biomineralization.
在硬骨鱼中，正常的平衡和听力依赖于内耳中的机械传感器。这些传感器包括从感觉毛细胞表面伸出并附着于生物矿化的“耳石”的肌动蛋白微绒毛和微管纤毛。耳石的数量、大小和位置受到严格的发育控制，但确保耳石在感觉上皮特定细胞顶部组装的机制尚不清楚。在此，我们证明纤毛运动对于正常的耳石组装和定位是必需的。通过体内视频显微镜观察，我们发现耳泡相对两极的运动性系纤毛产生流体涡旋，吸引耳石前体颗粒，从而使原本随机的分布产生偏向，引导耳石在系纤毛上局部播种。动力蛋白调节复合体和外臂动力蛋白亚基的独立敲低会破坏纤毛运动，导致耳石生物发生缺陷。这些结果证明了脊椎动物中动力蛋白调节复合体的必要性，并表明纤毛驱动的流动是控制耳石生物矿化的关键表观遗传因素。
