title: BMP signalling controls the construction of vertebrate mucociliary epithelia.
abstract: Despite the importance of mucociliary epithelia in animal physiology, the mechanisms controlling their establishment are poorly understood. Using the developing Xenopus epidermis and regenerating human upper airways, we reveal the importance of BMP signalling for the construction of vertebrate mucociliary epithelia. In Xenopus, attenuation of BMP activity is necessary for the specification of multiciliated cells (MCCs), ionocytes and small secretory cells (SSCs). Conversely, BMP activity is required for the proper differentiation of goblet cells. Our data suggest that the BMP and Notch pathways interact to control fate choices in the developing epidermis. Unexpectedly, BMP activity is also necessary for the insertion of MCCs, ionocytes and SSCs into the surface epithelium. In human, BMP inhibition also strongly stimulates the formation of MCCs in normal and pathological (cystic fibrosis) airway samples, whereas BMP overactivation has the opposite effect. This work identifies the BMP pathway as a key regulator of vertebrate mucociliary epithelium differentiation and morphogenesis.
authors.affiliation: Aix-Marseille Université, CNRS, IBDM, Marseille 13288, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Cibois
authors.affiliation: Aix-Marseille Université, CNRS, IBDM, Marseille 13288, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Luxardi
authors.affiliation: CNRS, IPMC, Sophia-Antipolis 06560, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Chevalier
authors.affiliation: Aix-Marseille Université, CNRS, IBDM, Marseille 13288, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Thomé
authors.affiliation: CNRS, IPMC, Sophia-Antipolis 06560, France University of Nice Sophia Antipolis (UNS), IPMC, Sophia-Antipolis 06560, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mercey
authors.affiliation: CNRS, IPMC, Sophia-Antipolis 06560, France University of Nice Sophia Antipolis (UNS), IPMC, Sophia-Antipolis 06560, France.
authors.forename: Laure-Emmanuelle
authors.initials: LE
authors.lastname: Zaragosi
authors.affiliation: CNRS, IPMC, Sophia-Antipolis 06560, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
authors.affiliation: Aix-Marseille Université, CNRS, IBDM, Marseille 13288, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pasini
authors.affiliation: CNRS, IPMC, Sophia-Antipolis 06560, France University of Nice Sophia Antipolis (UNS), IPMC, Sophia-Antipolis 06560, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Marcet
authors.affiliation: Aix-Marseille Université, CNRS, IBDM, Marseille 13288, France laurent.kodjabachian@univ-amu.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Kodjabachian
mesh_terms: D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D019070:Cell Lineage; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008168:Lung / Q000166:cytology; D012038:Regeneration; D015398:Signal Transduction; D014714:Vertebrates / Q000196:embryology* / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D029867:Xenopus Proteins
keywords: Airway; BMP; Epidermis; Human; Mucociliary epithelium; Multiciliogenesis; Notch; Xenopus