title: Modeling of the dorsal gradient across species reveals interaction between embryo morphology and Toll signaling pathway during evolution.
abstract: Morphogenetic gradients are essential to allocate cell fates in embryos of varying sizes within and across closely related species. We previously showed that the maternal NF-κB/Dorsal (Dl) gradient has acquired different shapes in Drosophila species, which result in unequally scaled germ layers along the dorso-ventral axis and the repositioning of the neuroectodermal borders. Here we combined experimentation and mathematical modeling to investigate which factors might have contributed to the fast evolutionary changes of this gradient. To this end, we modified a previously developed model that employs differential equations of the main biochemical interactions of the Toll (Tl) signaling pathway, which regulates Dl nuclear transport. The original model simulations fit well the D. melanogaster wild type, but not mutant conditions. To broaden the applicability of this model and probe evolutionary changes in gradient distributions, we adjusted a set of 19 independent parameters to reproduce three quantified experimental conditions (i.e. Dl levels lowered, nuclear size and density increased or decreased). We next searched for the most relevant parameters that reproduce the species-specific Dl gradients. We show that adjusting parameters relative to morphological traits (i.e. embryo diameter, nuclear size and density) alone is not sufficient to reproduce the species Dl gradients. Since components of the Tl pathway simulated by the model are fast-evolving, we next asked which parameters related to Tl would most effectively reproduce these gradients and identified a particular subset. A sensitivity analysis reveals the existence of nonlinear interactions between the two fast-evolving traits tested above, namely the embryonic morphological changes and Tl pathway components. Our modeling further suggests that distinct Dl gradient shapes observed in closely related melanogaster sub-group lineages may be caused by similar sequence modifications in Tl pathway components, which are in agreement with their phylogenetic relationships.
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Ambrosi
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Juan Sebastian
authors.initials: JS
authors.lastname: Chahda
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Koslen
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Hillel J
authors.initials: HJ
authors.lastname: Chiel
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio, United States of America; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Claudia Mieko
authors.initials: CM
authors.lastname: Mizutani
mesh_terms: D000818:Animals; D019295:Computational Biology; D003198:Computer Simulation; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000502:physiology*; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors