Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 307 (5708): 423-426

Copyright © 2005 by the American Association for the Advancement of Science

Mathematical Modeling of Planar Cell Polarity to Understand Domineering Nonautonomy

Keith Amonlirdviman,1 Narmada A. Khare,2 David R. P. Tree,2 Wei-Shen Chen,2 Jeffrey D. Axelrod,2*{dagger} Claire J. Tomlin1*{dagger}

Abstract: 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.

1 Department of Aeronautics and Astronautics, Stanford University, Stanford, CA 94305–4035, USA.
2 Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305–5324, USA.

Back to Top

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: tomlin{at} (C.J.T.); jaxelrod{at} (J.D.A.)

Polarity, cell division, and out-of-equilibrium dynamics control the growth of epithelial structures.
B. Cerruti, A. Puliafito, A. M. Shewan, W. Yu, A. N. Combes, M. H. Little, F. Chianale, L. Primo, G. Serini, K. E. Mostov, et al. (2013)
J. Cell Biol. 203, 359-372
   Abstract »    Full Text »    PDF »
Regulation of PCP by the Fat signaling pathway.
M. Matis and J. D. Axelrod (2013)
Genes & Dev. 27, 2207-2220
   Abstract »    Full Text »    PDF »
An intracellular partitioning-based framework for tissue cell polarity in plants and animals.
K. Abley, P. B. De Reuille, D. Strutt, A. Bangham, P. Prusinkiewicz, A. F. M. Maree, V. A. Grieneisen, and E. Coen (2013)
Development 140, 2061-2074
   Abstract »    Full Text »    PDF »
A Cul-3-BTB ubiquitylation pathway regulates junctional levels and asymmetry of core planar polarity proteins.
H. Strutt, E. Searle, V. Thomas-MacArthur, R. Brookfield, and D. Strutt (2013)
Development 140, 1693-1702
   Abstract »    Full Text »    PDF »
Structure-Function Dissection of the Frizzled Receptor in Drosophila melanogaster Suggests Different Mechanisms of Action in Planar Polarity and Canonical Wnt Signaling.
D. Strutt, D. Madder, V. Chaudhary, and P. J. Artymiuk (2012)
Genetics 192, 1295-1313
   Abstract »    Full Text »    PDF »
Dissecting the molecular bridges that mediate the function of Frizzled in planar cell polarity.
G. Struhl, J. Casal, and P. A. Lawrence (2012)
Development 139, 3665-3674
   Abstract »    Full Text »    PDF »
Wnt Signaling in Mammalian Development: Lessons from Mouse Genetics.
J. Wang, T. Sinha, and A. Wynshaw-Boris (2012)
Cold Spring Harb Perspect Biol 4, a007963
   Abstract »    Full Text »    PDF »
Wnt/PCP proteins regulate stereotyped axon branch extension in Drosophila.
J. Ng (2012)
Development 139, 165-177
   Abstract »    Full Text »    PDF »
Modelling planar polarity of epithelia: the role of signal relay in collective cell polarization.
I. Viktorinova, L. M. Pismen, B. Aigouy, and C. Dahmann (2011)
J R Soc Interface 8, 1059-1063
   Abstract »    Full Text »    PDF »
dachsous and frizzled contribute separately to planar polarity in the Drosophila ventral epidermis.
S. Donoughe and S. DiNardo (2011)
Development 138, 2751-2759
   Abstract »    Full Text »    PDF »
Principles of planar polarity in animal development.
L. V. Goodrich and D. Strutt (2011)
Development 138, 1877-1892
   Abstract »    Full Text »    PDF »
Wnt/PCP signaling controls intracellular position of MTOCs during gastrulation convergence and extension movements.
D. S. Sepich, M. Usmani, S. Pawlicki, and L. Solnica-Krezel (2011)
Development 138, 543-552
   Abstract »    Full Text »    PDF »
Modeling bistable cell-fate choices in the Drosophila eye: qualitative and quantitative perspectives.
T. G. W. Graham, S. M. A. Tabei, A. R. Dinner, and I. Rebay (2010)
Development 137, 2265-2278
   Abstract »    Full Text »    PDF »
Gradients and the Specification of Planar Polarity in the Insect Cuticle.
D. Strutt (2009)
Cold Spring Harb Perspect Biol 1, a000489
   Abstract »    Full Text »    PDF »
Planar Cell Polarity Signaling: The Developing Cell's Compass.
E. K. Vladar, D. Antic, and J. D. Axelrod (2009)
Cold Spring Harb Perspect Biol 1, a002964
   Abstract »    Full Text »    PDF »
Tuning the Activation Threshold of a Kinase Network by Nested Feedback Loops.
Q. A. Justman, Z. Serber, J. E. Ferrell Jr., H. El-Samad, and K. M. Shokat (2009)
Science 324, 509-512
   Abstract »    Full Text »    PDF »
Multiscale Modeling of Form and Function.
A. J. Engler, P. O. Humbert, B. Wehrle-Haller, and V. M. Weaver (2009)
Science 324, 208-212
   Abstract »    Full Text »    PDF »
Cell packing influences planar cell polarity signaling.
D. Ma, K. Amonlirdviman, R. L. Raffard, A. Abate, C. J. Tomlin, and J. D. Axelrod (2008)
PNAS 105, 18800-18805
   Abstract »    Full Text »    PDF »
From individual Wnt pathways towards a Wnt signalling network.
H. A Kestler and M. Kuhl (2008)
Phil Trans R Soc B 363, 1333-1347
   Abstract »    Full Text »    PDF »
The flare Gene, Which Encodes the AIP1 Protein of Drosophila, Functions to Regulate F-Actin Disassembly in Pupal Epidermal Cells.
N. Ren, J. Charlton, and P. N. Adler (2007)
Genetics 176, 2223-2234
   Abstract »    Full Text »    PDF »
Asymmetric Distribution of Prickle-Like 2 Reveals an Early Underlying Polarization of Vestibular Sensory Epithelia in the Inner Ear.
M. R. Deans, D. Antic, K. Suyama, M. P. Scott, J. D. Axelrod, and L. V. Goodrich (2007)
J. Neurosci. 27, 3139-3147
   Abstract »    Full Text »    PDF »
Order from disorder: Self-organization in mammalian hair patterning.
Y. Wang, T. Badea, and J. Nathans (2006)
PNAS 103, 19800-19805
   Abstract »    Full Text »    PDF »
Dynamic modelling and analysis of biochemical networks: mechanism-based models and model-based experiments.
N. A.W. van Riel (2006)
Brief Bioinform 7, 364-374
   Abstract »    Full Text »    PDF »
WNT and DKK Determine Hair Follicle Spacing Through a Reaction-Diffusion Mechanism.
S. Sick, S. Reinker, J. Timmer, and T. Schlake (2006)
Science 314, 1447-1450
   Abstract »    Full Text »    PDF »
A three-dimensional model of myxobacterial fruiting-body formation.
O. Sozinova, Y. Jiang, D. Kaiser, and M. Alber (2006)
PNAS 103, 17255-17259
   Abstract »    Full Text »    PDF »
Two separate molecular systems, Dachsous/Fat and Starry night/Frizzled, act independently to confer planar cell polarity..
J. Casal, P. A. Lawrence, and G. Struhl (2006)
Development 133, 4561-4572
   Abstract »    Full Text »    PDF »
A WNTer wonderland in Snowbird..
X. He and J. D. Axelrod (2006)
Development 133, 2597-2603
   Abstract »    Full Text »    PDF »
Separating the adhesive and signaling functions of the Fat and Dachsous protocadherins.
H. Matakatsu and S. S. Blair (2006)
Development 133, 2315-2324
   Abstract »    Full Text »    PDF »
Constructing quantitative models from qualitative mutant phenotypes: preferences in selecting sensory organ precursors.
C.-P. Hsu, P.-H. Lee, C.-W. Chang, and C.-T. Lee (2006)
Bioinformatics 22, 1375-1382
   Abstract »    Full Text »    PDF »
Genetic Evidence That Drosophila frizzled Controls Planar Cell Polarity and Armadillo Signaling by a Common Mechanism.
M. Povelones, R. Howes, M. Fish, and R. Nusse (2005)
Genetics 171, 1643-1654
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882