Nature：揭示内耳传感器的构成
2009-05-26 20:36:34   来源：   作者：  评论：0 点击：

研究人员使用高速高分辨率的摄像系统，来观察胚胎期斑马鱼正在发育的耳中纤毛的实时运动。这种鱼的发育经历了与人和其他脊椎动物类似的过程，使得其适合用于实验。

研究人员用荧光探针标记了斑马鱼中的纤毛，并用微观摄影术来记录纤毛和其他内耳结构。在对照组斑马鱼中，长纤毛像浆一般划动，形成漩涡，使得小的颗粒在漩涡周围转动。在适当位置聚集的大量旋转小颗粒就形成了内耳的晶体传感器。

论文通讯作者、加州大学洛杉矶分校副教授Kent Hill说：“之后我们阻止了控制动力蛋白（dynein）基因的表达，这种动力蛋白是一种极小的分子马达，它能驱动纤毛运动。当我们检查斑马鱼胚胎时，我们看到纤毛运动停止了。最终，小颗粒不再聚集在正确位置。耳晶体不仅出现在错误的位置，畸形，且大小也变得不正常。”

他说：“纤毛运动与耳晶体形成有关这一观点过去从未被实验验证过。我们的发现表明，耳内纤毛确实会运动，而且证明了纤毛运动是耳晶体聚集在正确位置所必需的。”

根据Hill的说法，这一发现有助于开发疗法，治疗听觉障碍和纤毛病变。纤毛病变是一种由纤毛功能不良造成的问题，可能会造成精子相关性不育、多囊肾病、肺和呼吸道问题以及脑肿胀等。

原始出处：

Nature，doi:10.1038/nature07520，Jessica R. Colantonio，Kent L. Hill

The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear

Jessica R. Colantonio1,5, Julien Vermot4,5, David Wu4, Adam D. Langenbacher2, Scott Fraser4, Jau-Nian Chen2,3 & Kent L. Hill1,3

1 Department of Microbiology, Immunology and Molecular Genetics,
2 Department of Molecular, Cell, and Developmental Biology
3 Molecular Biology Institute, University of California, Los Angeles, California 90095, USA
4 Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California 91125, USA
5 These authors contributed equally to this work.

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)1. 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.