title: Moesin is a major regulator of centrosome behavior in epithelial cells with extra centrosomes.
abstract: Centrosome amplification has severe consequences during development and is thought to contribute to a variety of diseases such as cancer and microcephaly. However, the adverse effects of centrosome amplification in epithelia are still not known. Here, we investigate the consequences of centrosome amplification in the Drosophila wing disc epithelium. We found that epithelial cells exhibit mechanisms of clustering but also inactivation of extra centrosomes. Importantly, these mechanisms are not fully efficient, and both aneuploidy and cell death can be detected. Epithelial cells with extra centrosomes generate tumors when transplanted into WT hosts and inhibition of cell death results in tissue over-growth and disorganization. Using SILAC-fly, we found that Moesin, a FERM domain protein, is specifically upregulated in wing discs with extra centrosomes. Moesin localizes to the centrosomes and mitotic spindle during mitosis, and we show that Moesin upregulation influences extra-centrosome behavior and robust bipolar spindle formation. This study provides a mechanistic explanation for the increased aneuploidy and transformation potential primed by centrosome amplification in epithelial tissues.
authors.affiliation: Institut Curie, CNRS UMR144, 12 Rue Lhomond, 75005 Paris, France.
authors.forename: Dora
authors.initials: D
authors.lastname: Sabino
authors.affiliation: Institut Curie, CNRS UMR144, 12 Rue Lhomond, 75005 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Gogendeau
authors.affiliation: Institut Curie, CNRS UMR144, 12 Rue Lhomond, 75005 Paris, France.
authors.forename: Davide
authors.initials: D
authors.lastname: Gambarotto
authors.affiliation: Institut Curie, CNRS UMR144, 12 Rue Lhomond, 75005 Paris, France.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Nano
authors.affiliation: Institut Curie, CNRS UMR144, 12 Rue Lhomond, 75005 Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Pennetier
authors.affiliation: Institut Curie, CNRS, LSMP, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Dingli
authors.affiliation: Institut Curie, CNRS, LSMP, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Arras
authors.affiliation: Institut Curie, CNRS, LSMP, 26 Rue d'Ulm, 75005 Paris, France.
authors.forename: Damarys
authors.initials: D
authors.lastname: Loew
authors.affiliation: Institut Curie, CNRS UMR144, 12 Rue Lhomond, 75005 Paris, France. Electronic address: renata.basto@curie.fr.
authors.forename: Renata
authors.initials: R
authors.lastname: Basto
mesh_terms: D000782:Aneuploidy; D000818:Animals; D016923:Cell Death; D018385:Centrosome / Q000378:metabolism*; D004330:Drosophila / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008840:Microfilament Proteins; C071058:moesin