title: Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers.
abstract: Cells in simple epithelia orient their mitotic spindles in the plane of the epithelium so that both daughter cells are born within the epithelial sheet. This is assumed to be important to maintain epithelial integrity and prevent hyperplasia, because misaligned divisions give rise to cells outside the epithelium. Here we test this assumption in three types of Drosophila epithelium; the cuboidal follicle epithelium, the columnar early embryonic ectoderm, and the pseudostratified neuroepithelium. Ectopic expression of Inscuteable in these tissues reorients mitotic spindles, resulting in one daughter cell being born outside the epithelial layer. Live imaging reveals that these misplaced cells reintegrate into the tissue. Reducing the levels of the lateral homophilic adhesion molecules Neuroglian or Fasciclin 2 disrupts reintegration, giving rise to extra-epithelial cells, whereas disruption of adherens junctions has no effect. Thus, the reinsertion of misplaced cells seems to be driven by lateral adhesion, which pulls cells born outside the epithelial layer back into it. Our findings reveal a robust mechanism that protects epithelia against the consequences of misoriented divisions.
authors.affiliation: The Gurdon Institute and the Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Dan T
authors.initials: DT
authors.lastname: Bergstralh
authors.affiliation: The Gurdon Institute and the Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Holly E
authors.initials: HE
authors.lastname: Lovegrove
authors.affiliation: The Gurdon Institute and the Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: St Johnston
mesh_terms: D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology / Q000378:metabolism*; D005260:Female; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D034622:RNA Interference; D014741:Video Recording
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D008164:Luminescent Proteins; D008565:Membrane Proteins; C411670:Mud protein, Drosophila; D009419:Nerve Tissue Proteins; C405164:Pins protein, Drosophila; C051642:fasciclin II; C098678:insc protein, Drosophila; C061745:Nrg protein, Drosophila