Multiciliated cells (MCCs) are required for driving fluid movement across epithelia. MCCs produce hundreds of centrioles that mature into basal bodies and nucleate motile cilia formation on the apical surface. Previous studies in Xenopus and humans have identified Mcidas (MCI) as a transcriptional regulator of MCC differentiation by association with the E2F family of DNA-binding proteins. The paralogous protein, GMNC, is also required for MCC development, although its precise role has been unclear. Now, Sudipto Roy and colleagues use a combination of genetic and biochemical approaches to understand the roles of MCI and GMNC in MCC differentiation. The authors show that MCC precursors are specified in Mci mutant mice, as determined by the expression of motile ciliogenesis factors, such as Foxj1. However, MCC precursors in Mci mutants lack multiple basal bodies, and genes involved in multiple basal body production are downregulated. In contrast, in Gmnc mutants, MCC precursors are not specified. Finally, the researchers demonstrate that MCI and GMNC interact with E2F4 and E2F5, respectively. These data suggest a biphasic model, facilitated by differential affinity for E2F co-factors, by which GMCN first specifies MCC precursors, and MCI regulates basal body production and multiciliation.
Mcidas and GMNC: not so similar for making cilia
Mcidas and GMNC: not so similar for making cilia. Development 15 March 2019; 146 (6): e0601. doi:
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