title: Interface Contractility between Differently Fated Cells Drives Cell Elimination and Cyst Formation.
abstract: Although cellular tumor-suppression mechanisms are widely studied, little is known about mechanisms that act at the level of tissues to suppress the occurrence of aberrant cells in epithelia. We find that ectopic expression of transcription factors that specify cell fates causes abnormal epithelial cysts in Drosophila imaginal discs. Cysts do not form cell autonomously but result from the juxtaposition of two cell populations with divergent fates. Juxtaposition of wild-type and aberrantly specified cells induces enrichment of actomyosin at their entire shared interface, both at adherens junctions as well as along basolateral interfaces. Experimental validation of 3D vertex model simulations demonstrates that enhanced interface contractility is sufficient to explain many morphogenetic behaviors, which depend on cell cluster size. These range from cyst formation by intermediate-sized clusters to segregation of large cell populations by formation of smooth boundaries or apical constriction in small groups of cells. In addition, we find that single cells experiencing lateral interface contractility are eliminated from tissues by apoptosis. Cysts, which disrupt epithelial continuity, form when elimination of single, aberrantly specified cells fails and cells proliferate to intermediate cell cluster sizes. Thus, increased interface contractility functions as error correction mechanism eliminating single aberrant cells from tissues, but failure leads to the formation of large, potentially disease-promoting cysts. Our results provide a novel perspective on morphogenetic mechanisms, which arise from cell-fate heterogeneities within tissues and maintain or disrupt epithelial homeostasis.
authors: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshadernerstrasse 2-4, 82152 Planegg-Martinsried, Germany.
authors: Christina
authors: C
authors: Bielmeier
authors: Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Strasse 38, 01187 Dresden, Germany; The Francis Crick Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors: Silvanus
authors: S
authors: Alt
authors: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshadernerstrasse 2-4, 82152 Planegg-Martinsried, Germany.
authors: Vanessa
authors: V
authors: Weichselberger
authors: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshadernerstrasse 2-4, 82152 Planegg-Martinsried, Germany.
authors: Marco
authors: M
authors: La Fortezza
authors: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshadernerstrasse 2-4, 82152 Planegg-Martinsried, Germany.
authors: Hartmann
authors: H
authors: Harz
authors: Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Strasse 38, 01187 Dresden, Germany.
authors: Frank
authors: F
authors: Jülicher
authors: Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Strasse 38, 01187 Dresden, Germany; The Francis Crick Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK. Electronic address: guillaume.salbreux@crick.ac.uk.
authors: Guillaume
authors: G
authors: Salbreux
authors: Ludwig-Maximilians-University Munich, Faculty of Biology, Grosshadernerstrasse 2-4, 82152 Planegg-Martinsried, Germany. Electronic address: classen@bio.lmu.de.
authors: Anne-Kathrin
authors: AK
authors: Classen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004330:Drosophila / Q000254:growth & development*; D029721:Drosophila Proteins / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D060227:Imaginal Discs / Q000254:growth & development*; D007814:Larva / Q000254:growth & development; D009024:Morphogenesis
chemical_list: D029721:Drosophila Proteins
keywords: actomyosin contractility; cell elimination; continuum mechanics; epithelial cyst; epithelium; physical modeling; tissue patterning; vertex model