纤毛作为细胞的“天线”，参与细胞内信号传导，在动物生殖发育和感知中发挥重要作用。纤毛缺陷可导致许多人类遗传疾病，统称为纤毛病。纤毛过渡纤维（Transition fibers）来源于母中心粒远端附属结构，位于纤毛入口处，是纤毛形成所需的关键结构。过渡纤维在纤毛形成起始阶段促进中心粒/基体在质膜上的锚定，在纤毛轴丝延伸阶段调控纤毛内转运复合体IFT的进出，但目前我们对其分子组成、形成调控及功能机理的认识仍处于起始阶段。申请人长期研究纤毛发生机制，发表了多篇相关文章。在前期的研究中，我们鉴定到了黑腹果蝇的4个过渡纤维蛋白，CEP164、FBF1、CEP89和SCLT1。本项目中，我们将以果蝇为模式，对这些基因的缺失突变体表型进行深入研究，并对它们之间的遗传学和物理学互作关系进行系统分析，以期解析它们在过渡纤维形成中的作用和在纤毛发生中的具体功能。项目对深入理解过渡纤维的形成和功能具有重要意义。

Cilia are microtubule-based hair like structures that are present on most eukaryotic cell surfaces. Cilia act as motile devices, or function as the cell’s sensory antennae to transduce many critical cellular signaling pathways. Dysfunction of cilia has been linked to a wide spectrum of human disorders, now collectively termed ciliopathies. Transition fibers locate below the transition zone, are nine-bladed propeller fibrous structures which are derived from the mother centriole distal appendages. It has been proposed that transition fibers promote the basal body docking during the ciliogenesis initiation stage, and they play critical roles in regulating the ciliary entry of IFT during the ciliary axoneme extension stage. But little is known about its formation and function, and their exact roles and the underlying molecular mechanisms remain poorly understood. The applicant has long experience in studying ciliogenesis, has published several cilia related papers. In this application, we will use the Drosophila model to dissect the function of the transition fiber protein CEP164, FBF1, CEP89 and SCLT1, and understand their physically and genetically interaction. Our proposed studies will shed light on our understating of the function and formation of ciliary transition fibers and their roles in ciliogenesis.