Mathematical modeling of planar cell polarity to understand domineering nonautonomy.
Planar cell polarity (PCP) signaling generates subcellular asymmetry along an axis orthogonal to the epithelial apical-basal axis. Through a poorly understood mechanism, cell clones that have mutations in some PCP signaling components, including some, but not all, alleles of the receptor frizzled, cause polarity disruptions of neighboring wild-type cells, a phenomenon referred to as domineering nonautonomy. Here, a contact-dependent signaling hypothesis, derived from experimental results, is shown by reaction-diffusion, partial differential equation modeling and simulation to fully reproduce PCP phenotypes, including domineering nonautonomy, in the Drosophila wing. The sufficiency of this model and the experimental validation of model predictions reveal how specific protein-protein interactions produce autonomy or domineering nonautonomy.
Amonlirdviman
Keith
K
Department of Aeronautics and Astronautics, Stanford University, Stanford, CA 94305-4035, USA.
Khare
Narmada A
NA
Tree
David R P
DR
Chen
Wei-Shen
WS
Axelrod
Jeffrey D
JD
Tomlin
Claire J
CJ
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D004058:Diffusion; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D025461:Feedback, Physiological; D051157:Frizzled Receptors; D008433:Mathematics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D014921:Wings, Animal / Q000166:cytology* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008565:Membrane Proteins; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; C111638:Vang protein, Drosophila; C058784:fz protein, Drosophila