title: GemC1 controls multiciliogenesis in the airway epithelium.
abstract: Multiciliated cells are terminally differentiated, post-mitotic cells that form hundreds of motile cilia on their apical surface. Defects in multiciliated cells lead to disease, including mucociliary clearance disorders that result from ciliated cell disfunction in airways. The pathway controlling multiciliogenesis, however, remains poorly characterized. We showed that GemC1, previously implicated in cell cycle control, is a central regulator of ciliogenesis. GemC1 is specifically expressed in ciliated epithelia. Ectopic expression of GemC1 is sufficient to induce early steps of multiciliogenesis in airway epithelial cells ex vivo, upregulating McIdas and FoxJ1, key transcriptional regulators of multiciliogenesis. GemC1 directly transactivates the McIdas and FoxJ1 upstream regulatory sequences, and its activity is enhanced by E2F5 and inhibited by Geminin. GemC1-knockout mice are born with airway epithelia devoid of multiciliated cells. Our results identify GemC1 as an essential regulator of ciliogenesis in the airway epithelium and a candidate gene for mucociliary disorders.
authors.affiliation: Laboratory of Biology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Arbi
authors.affiliation: Laboratory of Biology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Dafni-Eleftheria
authors.initials: DE
authors.lastname: Pefani
authors.affiliation: Laboratory of Physiology, School of Medicine University of Patras, Patras, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Kyrousi
authors.affiliation: Laboratory of Physiology, School of Medicine University of Patras, Patras, Greece.
authors.forename: Maria-Eleni
authors.initials: ME
authors.lastname: Lalioti
authors.affiliation: Laboratory of Physiology, School of Medicine University of Patras, Patras, Greece.
authors.forename: Argyro
authors.initials: A
authors.lastname: Kalogeropoulou
authors.affiliation: Laboratory of Biology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Anastasios D
authors.initials: AD
authors.lastname: Papanastasiou
authors.affiliation: Laboratory of Physiology, School of Medicine University of Patras, Patras, Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Taraviras
authors.affiliation: Laboratory of Biology, School of Medicine, University of Patras, Patras, Greece lygerou@med.upatras.gr.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Lygerou
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism; D050700:E2F5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D064248:Geminin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050700:E2F5 Transcription Factor; C490490:E2f5 protein, mouse; C481963:FOXJ1 protein, mouse; D051858:Forkhead Transcription Factors; D064248:Geminin; C000605589:Gmnc protein, mouse; C577997:Gmnn protein, mouse; C000605590:Mcidas protein, mouse; D009687:Nuclear Proteins
keywords: McIdas; cell cycle; ciliary epithelia; ciliopathies; respiratory disorders