Cytoplasmic MCIDAS organizes de novo centriole biogenesis in multiciliated cells

Multiciliated cells (MCCs) drive fluid flow over epithelia, but how their numerous basal bodies that seed multiciliation are generated remains heavily contended. Current view posits a de novo pathway, without mediation by parental centrioles or specialized organelles, the deuterosomes. Here, we report the intriguing finding that the MCC-specific master transcription factor, MCIDAS, moonlights in the cytoplasm to organize de novo centriole biogenesis. Like MCIDAS, its co-transcriptional regulators, E2F4 and E2F5, also undergo cytoplasmic accumulation during MCC differentiation, colocalizing with forming procentrioles. MCIDAS loss inhibited the cytoplasmic accumulation of the E2F proteins, and completely blocked centriole biogenesis. We also assembled a comprehensive list of MCIDAS targets, enriched in centriolar and ciliary genes as well as many others whose function in MCCs have not been explored. This resource will enable further exposition of MCC biology and the pathological mechanisms of motile ciliopathies like primary ciliary dyskinesia and other disorders involving MCC dysfunction.