Renal primary cilia are tiny hair-like organelles extending from the epithelial cell surface. Loss of cilia or ciliary protein causes renal cystic diseases. A renal cyst is a condition in which all or a part of the renal tubules are enlarged. The connection between primary cilia and renal cystic diseases are extensively studied, but the signaling molecules from cilia to cytoplasm/nuclei have not been identified. In this project, we challenge to clarify the signaling pathway from the primary cilia to the nucleus in the renal tubule maintenance.

Increased cell proliferation and randomly oriented cell division are commonly observed in renal cystic diseases. Experimentally stimulated cell proliferation in renal tubular cells causes the development of renal cysts, and disruption of the PCP pathway, which regulates the angle of cell division, and also develops renal cysts. However, PCP-related proteins are not localized to the primary cilia. Primary cilia typically form during G1 or G0 and disassemble around the time of mitosis. Therefore, analyses of cell cycle-dependent localization changes of ciliary and PCP-related proteins are required. We will also unveil the relationship between ciliary signaling and PCP pathway.

The reasons for the cell cycle-dependent cilium assembly and disassembly remain unclear. One probable explanation is that disassembly ensures proper formation of the mitotic spindle. Defects of cilium disassembly may contribute to abnormal cell division. If there might be the possibility that PCP proteins are involved in the cilium assembly /disassembly machinery, progress in this new research area would contribute to understanding of functional relationship between ciliary dysfunctions and abnormal cell proliferations such as cancer.