title: Fundamental physical cellular constraints drive self-organization of tissues.
abstract: Morphogenesis is driven by small cell shape changes that modulate tissue organization. Apical surfaces of proliferating epithelial sheets have been particularly well studied. Currently, it is accepted that a stereotyped distribution of cellular polygons is conserved in proliferating tissues among metazoans. In this work, we challenge these previous findings showing that diverse natural packed tissues have very different polygon distributions. We use Voronoi tessellations as a mathematical framework that predicts this diversity. We demonstrate that Voronoi tessellations and the very different tissues analysed share an overriding restriction: the frequency of polygon types correlates with the distribution of cell areas. By altering the balance of tensions and pressures within the packed tissues using disease, genetic or computer model perturbations, we show that as long as packed cells present a balance of forces within tissue, they will be under a physical constraint that limits its organization. Our discoveries establish a new framework to understand tissue architecture in development and disease.
authors.affiliation: Departamento de Biología Celular, Universidad de Sevilla and Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sánchez-Gutiérrez
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, UK.
authors.forename: Melda
authors.initials: M
authors.lastname: Tozluoglu
authors.affiliation: EMBL Heidelberg, Heidelberg, Germany.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Barry
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, London, UK.
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Departamento de Biología Celular, Universidad de Sevilla and Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain lmescudero-ibis@us.es.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Escudero
mesh_terms: D000818:Animals; D048430:Cell Shape; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002645:Chickens; D004330:Drosophila; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D006874:Hydrostatic Pressure; D008954:Models, Biological; D008962:Models, Theoretical; D009024:Morphogenesis
keywords: Voronoi diagrams; epithelial organization; morphogenesis; neuromuscular diseases