title: Modeling of gap gene expression in Drosophila Kruppel mutants.
abstract: The segmentation gene network in Drosophila embryo solves the fundamental problem of embryonic patterning: how to establish a periodic pattern of gene expression, which determines both the positions and the identities of body segments. The gap gene network constitutes the first zygotic regulatory tier in this process. Here we have applied the systems-level approach to investigate the regulatory effect of gap gene Kruppel (Kr) on segmentation gene expression. We acquired a large dataset on the expression of gap genes in Kr null mutants and demonstrated that the expression levels of these genes are significantly reduced in the second half of cycle 14A. To explain this novel biological result we applied the gene circuit method which extracts regulatory information from spatial gene expression data. Previous attempts to use this formalism to correctly and quantitatively reproduce gap gene expression in mutants for a trunk gap gene failed, therefore here we constructed a revised model and showed that it correctly reproduces the expression patterns of gap genes in Kr null mutants. We found that the remarkable alteration of gap gene expression patterns in Kr mutants can be explained by the dynamic decrease of activating effect of Cad on a target gene and exclusion of Kr gene from the complex network of gap gene interactions, that makes it possible for other interactions, in particular, between hb and gt, to come into effect. The successful modeling of the quantitative aspects of gap gene expression in mutant for the trunk gap gene Kr is a significant achievement of this work. This result also clearly indicates that the oversimplified representation of transcriptional regulation in the previous models is one of the reasons for unsuccessful attempts of mutant simulations.
authors.affiliation: Department of Computational Biology/Center for Advanced Studies, St. Petersburg State Polytechnical University, St. Petersburg, Russia.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kozlov
authors.forename: Svetlana
authors.initials: S
authors.lastname: Surkova
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Myasnikova
authors.forename: John
authors.initials: J
authors.lastname: Reinitz
authors.forename: Maria
authors.initials: M
authors.lastname: Samsonova
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D015870:Gene Expression; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008962:Models, Theoretical; D009154:Mutation
chemical_list: D029721:Drosophila Proteins; C497244:Kr protein, Drosophila; D051741:Kruppel-Like Transcription Factors