纤毛是以微管为基础形成的突出于细胞表面的细胞器，在胚胎发育、器官形成、细胞信号转导及人体生理功能维持等方面发挥着关键作用。我们最新研究发现前列腺素E2(PGE2)通过作用于纤毛定位的G蛋白偶联受体EP4调控纤毛生长和内脏器官左右不对称发育 (Nature Cell Biology, 2014)。PGE2-EP4信号主要通过腺苷酸环化酶(adenylate cyclase, AC) 激活下游cAMP/PKA信号。AC共有9种亚型，在调控纤毛生长和决定器官不对称发育中有哪些AC亚型参与，cAMP/PKA在其中是否具有作用仍不十分清楚。我们将基于前期研究成果，以斑马鱼和人类纤毛细胞为模型，筛选并确定PGE2-EP4信号在调控纤毛生长中的重要AC亚型，解析其定位于纤毛的特殊功能。同时，进一步探讨cAMP/PKA信号对纤毛生长的调控作用和机理。期望该研究能在纤毛与器官发育机制方面有所突破。

Cilium, a microtubule-based organelle that projects from the cell surface, has crucial roles in embryonic development, organ morphogenesis, cell signaling transduction and human physiology. We have recently identified that Prostaglandin E2(PGE2) signaling acts through a ciliary G-protein-coupled receptor, EP4, to promote ciliogenesis and regulate the laterality of visceral organs（Nature Cell Biology, 2014). PGE2-EP4 receptor signaling activates downstream cAMP/PKA signal through adenylate cyclase (AC). The AC family consists of 9 isoforms. It remain incompletely understood which AC isoforms are involved in ciliogenesis and left-right asymmetry and how AC plays essential roles in ciliogenesis. Based on the previous studies, we will determine the roles and mechanisms of AC isoforms in cilium formation and elongation. We will also investigate the effects of cAMP/PKA signaling during ciliogenesis. We hope the findings of this proposal will provide new insights into mechanisms of ciliogenesis and organ morphogenesis during development.