纤毛是以微管为主体伸向细胞外的突起，参与信号转导、器官形态发育及人体重要生理功能。纤毛如何形成、生长及调节组织器官发育是一个重要的科学问题。我们最新研究发现前列腺素信号通路能够调控纤毛形成和生长，并深刻影响心脏等器官的左右不对称发育 ( Nature Cell Biology,2014)。本项目采用遗传学与细胞和发育生物学相结合的方法，研究前列腺素入胞转运蛋白SLCO2A1在纤毛生长中的功能，探索SLCO2A1和ABCC4转运蛋白如何相互作用调节前列腺素水平与纤毛生长。在此基础上，我们将研究前列腺素G蛋白偶联受体在纤毛生长中的相互作用机理，解析其定位于纤毛膜的特殊功能；并在全细胞范围内寻找和发现参与纤毛内蛋白运输并依赖于前列腺素及其下游cAMP信号的磷酸化蛋白；同时，确定前列腺素信号在哺乳动物体内对纤毛生长及器官形成的调控机制与功能保守性。期望此项研究能在纤毛与器官发育机制方面有新的认识。

Cilium, a microtubule-based organelle that projects from the cell surface, has crucial roles in cell signaling transduction, organ morphogenesis and human physiology. How cilia form and grow, as well as regulate organ morphogenesis is an important question. We have recently identified that Prostaglandin (PG) signaling pathway is required for ciliogenesis and regulates the laterality of the heart and other organs（Nature Cell Biology,2014 ). We plan to study the roles of PG influx transporter SLCO2A1 during ciliogenesis; and understand whether SLCO2A1 and ABCC4, the PG efflux transporter, coordinate to control the extracellular PG during ciliogenesis. We will investigate the interactions of the Prostaglandin G-protein coupled receptors in cilia formation, and analyze their specific roles in cilia. Phosphoproteomics analyese will be conducted to identify axoneme proteins whose phosphorylation states are dependent on PG-cAMP signaling. Finally, we will test whether the ciligenic roles of PG signaling are conserved in mammalian animals. The findings of this proposal will provide new insights into mechanisms of ciliogenesis during development.