在斑马鱼中,同在人类和其他脊椎动物中一样,听力和平衡是由内耳中的机械传感器调控的。这些传感器由被称为“耳石”的、生物矿化的混合晶体组成。
Colantonio等人利用对斑马鱼胚胎的活体视频显微镜观测发现,由纤毛所产生的液流影响“耳石”的数量、生长和定位以及它们在发育过程中的矿化。用“吗琳代”反义低聚核甘酸所进行的基因剔除研究表明,纤毛运动需要动力蛋白调控复合物。所以,由纤毛驱动的流动在控制“耳石”生物矿化中似乎是一个关键的外源因子,而动力蛋白调控复合物亚单元则是人类纤毛疾病致病基因的候选物。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 457, 205-209 (8 January 2009) | doi:10.1038/nature07520
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.