title: Effects of growth and mutation on pattern formation in tissues.
abstract: In many developing tissues, neighboring cells enter different developmental pathways, resulting in a fine-grained pattern of different cell states. The most common mechanism that generates such patterns is lateral inhibition, for example through Delta-Notch coupling. In this work, we simulate growth of tissues consisting of a hexagonal arrangement of cells laterally inhibiting their neighbors. We find that tissue growth by cell division and cell migration tends to produce ordered patterns, whereas lateral growth leads to disordered, patchy patterns. Ordered patterns are very robust to mutations (gene silencing or activation) in single cells. In contrast, mutation in a cell of a disordered tissue can produce a larger and more widespread perturbation of the pattern. In tissues where ordered and disordered patches coexist, the perturbations spread mostly at boundaries between patches. If cell division occurs on time scales faster than the degradation time, disordered patches will appear. Our work suggests that careful experimental characterization of the disorder in tissues could pinpoint where and how the tissue is susceptible to large-scale damage even from single cell mutations.
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Mengel Pers
authors.forename: Sandeep
authors.initials: S
authors.lastname: Krishna
authors.forename: Sagar
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Simone
authors.initials: S
authors.lastname: Pigolotti
authors.forename: Vedran
authors.initials: V
authors.lastname: Sekara
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Semsey
authors.forename: Mogens H
authors.initials: MH
authors.lastname: Jensen
mesh_terms: D019521:Body Patterning / Q000502:physiology*; D002455:Cell Division; D002465:Cell Movement; D049109:Cell Proliferation; D060833:Cellular Microenvironment; D003198:Computer Simulation; D008954:Models, Biological; D009154:Mutation