纤毛是一种毛状细胞器，主要由基体和轴丝构成，在动物进化上保守而且功能重要。纤毛的基体是一个特化的中心粒，其上形成的数对微管由细胞膜包被形成天线状的轴丝。其中，多纤毛的发生还需要中心粒的大量扩增及保证细胞内纤毛的协调运动。纤毛可分为动纤毛和初级纤毛。动纤毛能驱动细胞或胞外液体的运动，而初级纤毛则是感觉器官，介导hedgehog等信号转导通路。纤毛功能的异常可导致一类被称为“纤毛病”的遗传疾病。我们在前期研究中，通过对处于多纤毛发生不同阶段的小鼠气管原代上皮细胞（MTEC）的基因表达谱分析和在斑马鱼胚胎中进行的纤毛相关基因筛选等发现了一系列重要的新的功能基因。本项目拟聚焦中心粒扩增、基体极性形成、轴丝生长等多纤毛发生中的重要科学问题，利用超高分辨率荧光显微术等手段以及细胞、组织、斑马鱼和基因敲除小鼠等模型深入探索并阐述纤毛发生及其行使功能的新机理，发现新的纤毛病病征及相关基因。

Cilium is a hair-like organelle mainly composed of basal body and axoneme. It is highly conserved in animal evolution and capable of important functions. The basal body is a specialized centriole, from which multiple bundles of microtubules grow to form the antennae-like axoneme. During the genesis of multicilia, centrioles are markedly amplified and certain mechanisms are also required to assure the coordinated movement among different cilia. Cilia can be either motile or immotile. Motile cilia propel cell movement or luminal liquid flow, whereas immotile, or primary, cilium serves as a sensory organ and mediates multiple signaling pathways. Dysfunctions of cilia have been found to cause a wide variety of genetic disorders collectively named “ciliophathy”. We have analyzed gene expression profiles at different stages of ciliogenesis by using cultured primary mouse airway epithelial cells (MTEC) and gene chip assays and performed a functional screen using zebrafish embryos and microinjection of morpholino oligos. A series of important new genes involved in distinct aspects of ciliogenesis have thus been identified. In this proposal, we will use tools such as the cutting-edge super-resolution light microscopy and model systems of cells, tissues, and animals to continue our explorations on mechanisms of ciliogenesis, with particular focuses on centriole amplification, basal body polarization, and axonemal growth. Our aim is to understand how our identified genes participate in multicilia formation, cilia functions, and possibly ciliopathy.