Gmnc Is a Master Regulator of the Multiciliated Cell Differentiation Program

Feng Zhou, Vijay Narasimhan, Mohammad Shboul, Yan Ling Chong, Bruno Reversade, Sudipto Roy

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


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.
Original languageEnglish (US)
Pages (from-to)3267-3273
Number of pages7
JournalCurrent Biology
Issue number24
StatePublished - Dec 21 2015
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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