專題:Nature報導
在斑馬魚中,同在人類和其他脊椎動物中一樣,聽力和平衡是由內耳中的機械傳感器調控的。這些傳感器由被稱為「耳石」的、生物礦化的混合晶體組成。
Colantonio等人利用對斑馬魚胚胎的活體視頻顯微鏡觀測發現,由纖毛所產生的液流影響「耳石」的數量、生長和定位以及它們在發育過程中的礦化。用「嗎琳代」反義低聚核甘酸所進行的基因剔除研究表明,纖毛運動需要動力蛋白調控複合物。所以,由纖毛驅動的流動在控制「耳石」生物礦化中似乎是一個關鍵的外源因子,而動力蛋白調控複合物亞單元則是人類纖毛疾病致病基因的候選物。(生物谷Bioon.com)
生物谷推薦原始出處:
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.