title: A discrete model of Drosophila eggshell patterning reveals cell-autonomous and juxtacrine effects.
abstract: The Drosophila eggshell constitutes a remarkable system for the study of epithelial patterning, both experimentally and through computational modeling. Dorsal eggshell appendages arise from specific regions in the anterior follicular epithelium that covers the oocyte: two groups of cells expressing broad (roof cells) bordered by rhomboid expressing cells (floor cells). Despite the large number of genes known to participate in defining these domains and the important modeling efforts put into this developmental system, key patterning events still lack a proper mechanistic understanding and/or genetic basis, and the literature appears to conflict on some crucial points. We tackle these issues with an original, discrete framework that considers single-cell models that are integrated to construct epithelial models. We first build a phenomenological model that reproduces wild type follicular epithelial patterns, confirming EGF and BMP signaling input as sufficient to establish the major features of this patterning system within the anterior domain. Importantly, this simple model predicts an instructive juxtacrine signal linking the roof and floor domains. To explore this prediction, we define a mechanistic model that integrates the combined effects of cellular genetic networks, cell communication and network adjustment through developmental events. Moreover, we focus on the anterior competence region, and postulate that early BMP signaling participates with early EGF signaling in its specification. This model accurately simulates wild type pattern formation and is able to reproduce, with unprecedented level of precision and completeness, various published gain-of-function and loss-of-function experiments, including perturbations of the BMP pathway previously seen as conflicting results. The result is a coherent model built upon rules that may be generalized to other epithelia and developmental systems.
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal; Yamaguchi University, Faculty of Science, Yoshida, Yamaguchi City, Yamaguchi, Japan.
authors.forename: Adrien
authors.initials: A
authors.lastname: Fauré
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Barbara M I
authors.initials: BM
authors.lastname: Vreede
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal; Universidade de Lisboa, Faculdade de Ciências, Departamento de Biologia Animal, Campo Grande, Lisboa, Portugal.
authors.forename: Elio
authors.initials: E
authors.lastname: Sucena
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Claudine
authors.initials: C
authors.lastname: Chaouiya
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D019295:Computational Biology; D003198:Computer Simulation; D004331:Drosophila melanogaster / Q000502:physiology*; D004527:Egg Proteins / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D009865:Oocytes / Q000166:cytology; D009866:Oogenesis / Q000502:physiology; D015398:Signal Transduction; D012984:Software; D014817:Vitelline Membrane / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D004527:Egg Proteins; C015753:chorion proteins; D004815:Epidermal Growth Factor