Gene circuit analysis of the terminal gap gene huckebein

• Published in: PLoS computational biology 2009-10, Vol.5 (10), p.e1000548-e1000548
• Main Authors: Ashyraliyev, Maksat, Siggens, Ken, Janssens, Hilde, Blom, Joke, Akam, Michael, Jaeger, Johannes
• Format: Article
• Language: English
• Subjects: Algorithms; Animals; Biology; Computational Biology/Systems Biology; Computational Biology/Transcriptional Regulation; Computer Simulation; Confidence intervals; Developmental biology; Developmental Biology/Pattern Formation; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila; Drosophila melanogaster; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Embryo, Nonmammalian - metabolism; Embryonic development; Gene expression; Gene Regulatory Networks - physiology; Genetics and Genomics/Gene Expression; Immunohistochemistry; Least-Squares Analysis; Life sciences; Mathematical models; Mathematics; Models, Genetic; Mutation; Proteins; ras GTPase-Activating Proteins - genetics; ras GTPase-Activating Proteins - metabolism; Studies; Systems Biology - methods; Transcription Factors
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1000548

The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network.