Transcriptional regulation of CCNO during the formation of multiple motile cilia.

ABSTRACT

Primary ciliary dyskinesia (PCD) is a group of genetically heterogeneous disorders characterized by clinical manifestations resulting from abnormal ciliary motility. Mutations in critical genes, such as Cyclin O (CCNO), have been associated with severe respiratory disease, though limited data are currently available. Here we show that CCNO deficient ciliated cells can only form a reduced number of fully functional centrioles that can mature into ciliated basal bodies, and their transport and anchoring to the top of the plasma membrane are abnormal. Furthermore, we observed that CCNO localizes not only in the cytoplasm but also in the nucleus during the early stages of ciliogenesis, and this dual localization persists into adulthood. Transcriptome analysis revealed downregulation of genes involved in cilia assembly and movement, along with altered transcription factors associated with ciliation upon CCNO depletion. These findings indicate that CCNO may serve as a key regulator in the transcriptional regulation of multiciliogenesis.