运动纤毛／鞭毛是一种高度保守的毛发状结构，它的轴丝主要由9+2的微管组成。目前的研究认为在纤毛运动过程中，中央微管产生运动的初始信号，通过辐射轴传递到动力蛋白臂，调控纤毛摆动。中央微管的结构和功能缺陷都会影响纤毛运动，导致原发性纤毛运动障碍综合征。虽然目前通过对衣藻的中央微管的研究，我们对中央微管的功能和组成有了一定的了解，但是中央微管的组装机制仍不清楚。此外，目前的研究也提示哺乳动物动纤毛的中央微管组装的分子机理与衣藻有很大的不同。在我们的前期研究中，我们发现了哺乳动物动纤毛中央微管发生必需的基因，wdr47，它的敲除导致动纤毛中央微管缺失，纤毛运动异常。以wdr47及其基因敲除小鼠为切入点，本项目将筛选哺乳动物中央微管组装及其功能相关的重要基因，深入研究中央微管组装的分子机理。

Motile cilia/flagella are evolutionarily conserved hair-like structures and their axonemes are composed of 9+2 microtubules. It is believed that the central apparatus generates the initiate signals and transmits them to dynein arms through interaction with radial spokes and subsequently the dynein arms slide along the adjacent MT doublets to generate the cilia motility. Therefore, defects in both structure and function of the central apparatus affect cilia beating and cause primary ciliary dyskinesia, an autosomal recessive disorder. The studies from Chlymodomonas give an insight into the structure and components of the central apparatus, however, the molecular mechanism underlying central apparatus assembly remains elusive. Furthermore, various studies also reveal the significant differences in the assembly of the central apparatus between Chlamydomonas and mammals. In our previous studies, we identified a WD40 and LisH motif containing protein, wdr47, which plays a critical role in the assembly of the central pair of MTs. Knockout of wdr47 results in loss of the central pair of MTs and change of cilia beating patterning. In this proposal, we will screen for the key gene(s) functioning in the assembly of the central apparatus and explore its/their function and relationship(s) between these genes and wdr47. Finally, we will uncover the underlying molecular mechanism of the central apparatus assembly in mammals.