Моделирование динамики экспрессии генов gap в зародыше плодовой мушки при изменении количества копий морфогена
Peter the Great St. Petersburg Polytechnic University, St. Petersburg 195251, Russia, Engelhardt Institute of Molecular Biology, RAS, Moscow, 119991, Russia Ioffe Institute, St. Petersburg, 194021, Russia
Bicoid (Bcd) as а classic morphogen plays a key role in the expression of segmentation genes in Drosophila embryo. The segmentation gene network controls the determination of the fruit fly segments during the blastoderm stage, just before the onset of gastrulation. We applied the systems-level approach to understand the spatial dynamics of gap gene expression domains under different Bicoid dosages using the data on the hb anterior domain shifts.
We obtained new parameters of the sequence-based model [1, 2] that uses thermodynamic approach to describe the target gene expression at the RNA level and two sets of reaction-diffusion differential equations for mRNA and protein concentrations to describe the dynamics of the system. The gap gene network consists of 4 gap genes – hb, Kr, gt, and kni – under control of 12 transcription factors (TF) – the products of hb, Kr, gt, kni, bcd, tll, cad, hkb, cic, slp, and run genes and pioneer factor Zelda. We predicted TF binding sites in the potential regulatory region from 12Kbp upstream to 6Kbp downstream of transcription start site for each gene using enhanced dinucleotide positional weight matrices. The unknown model parameters were obtained with the DEEP method by fitting the model solutions to both expression patterns of gap genes and data on the hb anterior domain shifts in embryos with varying Bcd concentration.
We compared the developed sequence-based model with the phenomenological model  that uses the reaction-diffusion differential equations and the matrix of regulatory coefficients characterizing the action of regulators on their targets. Both models successfully reproduce the characteristic features of experimental data. The sequence-based model reproduces the spatial dynamics of the hb anterior expression domain more precisely.
Thе study was supported by the RFBR grant 14-04-01522 and the "5-100-2020" Program of the Ministry of Education and Science of the Russian Federation.
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2. K. Kozlov, V. Gursky, I. Kulakovskiy, M. Samsonova (2014). Sequence-Based Model of Gap Gene Regulatory Network. BMC Genomics, 15(Suppl 12):S6
3. Andreev, S. A., Samsonova, M. G., and Gursky, V. V. (2015). Modeling of the Drosophila gap-gene network with the variation of the Bcd morphogen. Biophysics, 60(2), 173–180.