title: Robustness and stability of the gene regulatory network involved in DV boundary formation in the Drosophila wing.
abstract: Gene regulatory networks have been conserved during evolution. The Drosophila wing and the vertebrate hindbrain share the gene network involved in the establishment of the boundary between dorsal and ventral compartments in the wing and adjacent rhombomeres in the hindbrain. A positive feedback-loop between boundary and non-boundary cells and mediated by the activities of Notch and Wingless/Wnt-1 leads to the establishment of a Notch dependent organizer at the boundary. By means of a Systems Biology approach that combines mathematical modeling and both in silico and in vivo experiments in the Drosophila wing primordium, we modeled and tested this regulatory network and present evidence that a novel property, namely refractoriness to the Wingless signaling molecule, is required in boundary cells for the formation of a stable dorsal-ventral boundary. This new property has been validated in vivo, promotes mutually exclusive domains of Notch and Wingless activities and confers stability to the dorsal-ventral boundary. A robustness analysis of the regulatory network complements our results and ensures its biological plausibility.
authors.affiliation: Centre especial de Recerca en Química Teòrica (CeRQT), Parc Científic de Barcelona, Barcelona, Spain. jbuceta@pcb.ub.es
authors.forename: Javier
authors.initials: J
authors.lastname: Buceta
authors.forename: Héctor
authors.initials: H
authors.lastname: Herranz
authors.forename: Oriol
authors.initials: O
authors.lastname: Canela-Xandri
authors.forename: Ramon
authors.initials: R
authors.lastname: Reigada
authors.forename: Francesc
authors.initials: F
authors.lastname: Sagués
authors.forename: Marco
authors.initials: M
authors.lastname: Milán
mesh_terms: D000818:Animals; D004330:Drosophila / Q000033:anatomy & histology / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics; D005246:Feedback; D005786:Gene Expression Regulation; D006706:Homeostasis; D008024:Ligands; D014176:Protein Biosynthesis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D014714:Vertebrates / Q000033:anatomy & histology / Q000235:genetics; D014921:Wings, Animal / Q000033:anatomy & histology* / Q000254:growth & development; D051155:Wnt1 Protein / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D008024:Ligands; D011956:Receptors, Cell Surface; D051155:Wnt1 Protein; C074622:wg protein, Drosophila