Gmnc Is a Master Regulator of the Multiciliated Cell Differentiation Program
Multiciliated cells (MCCs) differentiate hundreds of motile cilia that generate mechanical force required to drive fluid movement over epithelia [1, 2]. For example, metachronal beating of MCC cilia in the mammalian airways clears mucus that traps inhaled pathogens and pollutants. Consequently, abno...
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Published in | Current biology Vol. 25; no. 24; pp. 3267 - 3273 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
21.12.2015
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Subjects | |
Online Access | Get full text |
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Summary: | Multiciliated cells (MCCs) differentiate hundreds of motile cilia that generate mechanical force required to drive fluid movement over epithelia [1, 2]. For example, metachronal beating of MCC cilia in the mammalian airways clears mucus that traps inhaled pathogens and pollutants. Consequently, abnormalities in MCC differentiation or ciliary motility have been linked to an expanding spectrum of human airway diseases [3–6]. The current view posits that MCC precursors are singled out by the inhibition of Notch signaling. MCC precursors then support an explosive production of basal bodies, which migrate to the apical surface, dock with the plasma membrane, and seed the growth of multiple motile cilia. At the center of this elaborate differentiation program resides the coiled-coil-containing protein Multicilin, which transcriptionally activates genes for basal body production and the gene for FoxJ1, the master regulator for basal body docking, cilia formation, and motility [7, 8]. Here, using genetic analysis in the zebrafish embryo, we discovered that Gmnc is a novel determinant of the MCC fate. Like Multicilin, Gmnc is a coiled-coil-containing protein of the Geminin family. We show that Gmnc functions downstream of Notch signaling, but upstream of Multicilin in the developmental pathway controlling MCC specification. Moreover, we find that loss of Gmnc in Xenopus embryos also causes loss of MCC differentiation and that overexpression of the protein is sufficient to induce supernumerary MCCs. Together, our data identify Gmnc as an evolutionarily conserved master regulator functioning at the top of the hierarchy of transcription factors involved in MCC differentiation.
•Motile cilia on multiciliated cells (MCCs) function in fluid clearance•The coiled-coil protein Gmnc is a novel determinant of MCC fate•Gmnc functions downstream of Notch signaling but upstream of Multicilin•Gmnc is a master regulator, being required and sufficient for MCC specification
Multiciliated cells (MCCs) bear hundreds of motile cilia that beat to drive fluid movement. For instance, MCCs function as janitors of the airways, where they promote mucus clearance. Using genetic analysis in zebrafish and Xenopus, Zhou et al. report that the coiled-coil protein GMNC is a novel determinant and key regulator of MCC fate. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0960-9822 1879-0445 |
DOI: | 10.1016/j.cub.2015.10.062 |