Oishi Isao, Kawakami Yasuhiko, Raya Angel, Callol-Massot Carles, Izpisúa Belmonte Juan Carlos
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nat Genet. 2006 Nov;38(11):1316-22. doi: 10.1038/ng1892. Epub 2006 Oct 1.
Primary cilia are microtubule-based organelles that project from the surface of nearly every animal cell. Although important functions of primary cilia in morphogenesis and tissue homeostasis have been identified, the mechanisms that control the formation of primary cilia are not understood. Here we characterize a zebrafish gene, termed duboraya (dub), that is essential for ciliogenesis. Knockdown of dub in zebrafish embryos results in both defects in primary cilia formation in Kupffer's vesicle and randomization of left-right organ asymmetries. We show that, at the molecular level, the function of dub in ciliogenesis is regulated by phosphorylation, which in turn depends on Frizzled-2-mediated noncanonical Wnt signaling. We also provide evidence that, at the cellular level, dub function is essential for actin organization in the cells lining Kupffer's vesicle. Taken together, our findings identify a molecular factor that links noncanonical Wnt signaling with the control of left-right axis specification, and provide an entry point for analyzing the mechanisms that regulate primary cilia formation.
初级纤毛是基于微管的细胞器，从几乎每个动物细胞的表面伸出。尽管已经确定了初级纤毛在形态发生和组织稳态中的重要功能，但控制初级纤毛形成的机制仍不清楚。在这里，我们对一个名为duboraya（dub）的斑马鱼基因进行了表征，该基因对纤毛发生至关重要。在斑马鱼胚胎中敲低dub会导致库普弗小泡中初级纤毛形成缺陷以及左右器官不对称性的随机化。我们表明，在分子水平上，dub在纤毛发生中的功能受磷酸化调节，而磷酸化又依赖于卷曲蛋白-2介导的非经典Wnt信号传导。我们还提供证据表明，在细胞水平上，dub功能对于库普弗小泡内衬细胞中的肌动蛋白组织至关重要。综上所述，我们的研究结果确定了一个将非经典Wnt信号与左右轴特化控制联系起来的分子因子，并为分析调节初级纤毛形成的机制提供了一个切入点。
