Systematic analysis of Rfx2 target genes in vertebrate multiciliated cells
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Multiciliated cells (MCCs) drive directional fluid flow in diverse tubular organs and are essential for development and homeostasis of the vertebrate central nervous system, airway, and reproductive tracts. These cells are characterized by dozens or hundreds of long, motile cilia that beat in a coordinated and polarized manner. In recent years, genomic studies have not only elucidated the transcriptional hierarchy for MCC specification, but also identified myriad new proteins that govern MCC ciliogenesis, cilia beating, or cilia polarization. Interestingly, this burst of genomic data has also highlighted the obvious importance of the “ignorome,” that large fraction of vertebrate genes that remain only poorly characterized. Understanding the function of novel proteins with little prior history of study presents a special challenge, especially when faced with large numbers of such proteins. Here, we explored the MCC ignorome by defining the subcellular localization of 260 poorly defined proteins in vertebrate MCCs in vivo. Based on this localization data, we selected some targets of MCC ignorome for further functional studies because they could possibly play key roles in the regulation of ciliogenesis. We characterized Myo5c as the motor for basal body apical migration, vi Arhgef18 as the RhoA signaling activator at the basal bodies, and Dennd2b as a regulator of actin network formation and ciliogenesis. All of these findings have deepened our understanding about molecular mechanisms of related cellular process. This study exemplifies the power of high content protein localization screening as the bridging step between large-scale omics data and functional study of specific proteins.