Effects of Growth and Mutation on Pattern Formation in Tissues

TY - JOUR

T1 - Effects of Growth and Mutation on Pattern Formation in Tissues

AU - Mengel, Anne Benedicte

AU - Krishna, Sandeep

AU - Chakraborty, Sagar

AU - Pigolotti, Simone

AU - Sekara, Vedran

AU - Semsey, Szabolcs

AU - Jensen, Mogens Høgh

PY - 2012/11/7

Y1 - 2012/11/7

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pone.0048772

DO - 10.1371/journal.pone.0048772

M3 - Journal article

C2 - 23144963

SN - 1932-6203

VL - 7

SP - e48772

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 11

ER -