title: Pattern formation of Rho GTPases in single cell wound healing.
abstract: The Rho GTPases-Rho, Rac, and Cdc42-control an enormous variety of processes, many of which reflect activation of these GTPases in spatially confined and mutually exclusive zones. By using mathematical models and experimental results to establish model parameters, we analyze the formation and segregation of Rho and Cdc42 zones during Xenopus oocyte wound repair and the role played by Abr, a dual guanine nucleotide exchange factor-GTPase-activating protein, in this process. The Rho and Cdc42 zones are found to be best represented as manifestations of spatially modulated bistability, and local positive feedback between Abr and Rho can account for the maintenance and dynamic properties of the Rho zone. In contrast, the invocation of an Abr-independent positive feedback loop is required to account for Cdc42 spatial bistability. In addition, the model replicates the results of previous in vivo experiments in which Abr activity is manipulated. Further, simulating the model with two closely spaced wounds made nonintuitive predictions about the Rho and Cdc42 patterns; these predictions were confirmed by experiment. We conclude that the model is a useful tool for analysis of Rho GTPase signaling and that the Rho GTPases can be fruitfully considered as components of intracellular pattern formation systems.
authors.affiliation: Department of Mathematics, University of British Columbia, Vancouver, BC, Canada. corymsimon@gmail.com
authors.forename: Cory M
authors.initials: CM
authors.lastname: Simon
authors.forename: Emily M
authors.initials: EM
authors.lastname: Vaughan
authors.forename: William M
authors.initials: WM
authors.lastname: Bement
authors.forename: Leah
authors.initials: L
authors.lastname: Edelstein-Keshet
mesh_terms: D000818:Animals; D019521:Body Patterning; D002478:Cells, Cultured; D003198:Computer Simulation; D004795:Enzyme Stability; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D009865:Oocytes / Q000201:enzymology / Q000502:physiology; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D059010:Single-Cell Analysis; D059008:Time-Lapse Imaging; D014945:Wound Healing; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis; D020742:rhoA GTP-Binding Protein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D029867:Xenopus Proteins; C559910:Cdc42 protein, Xenopus; D020559:Monomeric GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein