title: Modulation of junction tension by tumor suppressors and proto-oncogenes regulates cell-cell contacts.
abstract: Tumor suppressors and proto-oncogenes play crucial roles in tissue proliferation. Furthermore, de-regulation of their functions is deleterious to tissue architecture and can result in the sorting of somatic rounded clones minimizing their contact with surrounding wild-type (wt) cells. Defects in the shape of somatic clones correlate with defects in proliferation, cell affinity, cell-cell adhesion, oriented cell division and cortical contractility. Combining genetics, live-imaging, laser ablation and computer simulations, we aim to analyze whether distinct or similar mechanisms can account for the common role of tumor suppressors and proto-oncogenes in cell-cell contact regulation. In Drosophila epithelia, the tumor suppressors Fat (Ft) and Dachsous (Ds) regulate cell proliferation, tissue morphogenesis, planar cell polarity and junction tension. By analyzing the evolution over time of ft mutant cells and clones, we show that ft clones reduce their cell-cell contacts with the surrounding wt tissue in the absence of concomitant cell divisions and over-proliferation. This contact reduction depends on opposed changes of junction tensions in the clone bulk and its boundary with neighboring wt tissue. More generally, either clone bulk or boundary junction tension is modulated by the activation of Yorkie, Myc and Ras, yielding similar contact reductions with wt cells. Together, our data highlight mechanical roles for proto-oncogene and tumor suppressor pathways in cell-cell interactions.
authors.affiliation: Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris, Cedex 05, France floris.bosveld@curie.fr yohanns.bellaiche@curie.fr.
authors.forename: Floris
authors.initials: F
authors.lastname: Bosveld
authors.affiliation: Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Guirao
authors.affiliation: Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Rivière
authors.affiliation: Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bonnet
authors.affiliation: Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris, Cedex 05, France.
authors.forename: François
authors.initials: F
authors.lastname: Graner
authors.affiliation: Polarity, Division and Morphogenesis Team, Institut Curie, CNRS UMR 3215, INSERM U934, 26 rue d'Ulm, 75248 Paris, Cedex 05, France floris.bosveld@curie.fr yohanns.bellaiche@curie.fr.
authors.forename: Yohanns
authors.initials: Y
authors.lastname: Bellaïche
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002455:Cell Division; D016764:Cell Polarity; D049109:Cell Proliferation; D048430:Cell Shape; D002999:Clone Cells; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D007365:Intercellular Junctions / Q000378:metabolism; D009154:Mutation; D009218:Myosins / Q000378:metabolism; D011519:Proto-Oncogenes; D059008:Time-Lapse Imaging; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins; C492999:dachs protein, Drosophila; C472307:ft protein, Drosophila; D009218:Myosins
keywords: Clone shape; Fat/Dachsous and Hippo pathways; Junction tension; Myc; Myosins; Ras