FOR20在动物胚胎发育及纤毛生长过程中的作用及分子机制研究

纤毛是一种基于微管的突出于细胞表面的细胞器，在动物胚胎发育等一系列基本生命活动中发挥重要作用，其结构或功能异常会导致多种疾病。目前研究显示，进化上保守的中心体蛋白FOR20可能影响细胞纤毛的生长过程；然而，FOR20在整体动物中的生理功能及其对纤毛调控的具体分子机制仍不清楚。我们的前期研究发现，在斑马鱼中下调FOR20不仅会导致肾管和Kuppfer’s vesicle内纤毛数量减少及长度变短，而且还诱导一系列纤毛异常的相关表型。进一步研究显示，FOR20可与纤毛调节蛋白CEP290在中心体上相互作用。这些结果提示，FOR20可能通过调节由中心体衍生的纤毛基体的成熟而影响纤毛生长，进而调控动物胚胎发育过程。本项目拟在动物、细胞及分子水平，系统探讨FOR20在胚胎早期发育及纤毛生长过程中的作用及分子调节机制，为人类纤毛相关疾病的诊治提供新的理论依据。

Cilia are microtubule -based organelle that project from cell membrane, which paly an important role in embryonic development and other basic life processes. Disorders of cilia structure and function contribute to numerous of diseases. Recent data show that the centrosomal protein FOR20 (FOP-related protein of 20 kDa) may influence ciliogenesis. However, the function of FO20 in vivo, and how it is involved in ciliogenesis is largely unknown. Our previous work found that the number and length of cilium in pronephric ducts and Kuppfer’s vesicles were significantly decreased when FOR20 knockdown in zebrafish. Meanwhile, FOR20 knockdown resulted in classical cilia-defects phenotype. Moreover, we found that FOR20 interacts with ciliary protein CEP290. These results indicated that FOR20 may involved in ciliogensis by regulating maturation of basal bodies which are derived from centrsomes, and participated in embryogenesis. In this proposal, we will systematically characterize the biological function of FOR20 in ciliogenesis, and to elucidate its possible molecular mechanism, which may provide potential therapeutic targets for ciliopathies.