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.

Sequential construction of a model for modular gene expression control, applied to spatial patterning of theDrosophilagenehunchback

“…and relative strengths of e®ects on hb transcription that best¯t the experimental pattern. We focus on expression of the PS4 stripe: computations are run on the interval 18-65%EL, which does not include the posterior stripe (and which is likely under di®erent TF controls 12,27,36 ). For this, we use the approximation that P1 control is through the stripe element only, i.e.…”

“…Gt and Kni shift in Kr À mutants; for modeling these cases, we used input data from Ref. 36. Initial values of hb P1 and P2 mRNA were set to zero.…”

Experimental and Modeling Approaches for Understanding the Effect of Gene Expression Noise in Biological Development

“…For example, parameter searches with the gene interaction matrix approach of Mjolsness et al and Reinitz and Sharp [8,9] found classes of networks for wild-type [10] and mutant [11][12][13] gap-gene patterns. Such potential mechanisms can be further screened for robustness to extrinsic variability, such as to Bcd gradient variability [11,12].…”

Mathematical model based on the Jeffreys type equation for description of gene expression

“…The equation (1) is widely applied for description of diffusive transport, e.g., of protein transfer, that are synthesized by gap genes (the gene expression process) in D.melanogaster embryo at the early stages of development [10,13]. However, it is well known, that the model (1) has a remarkable disadvantage [1]: the propagation velocity of perturbations is infinite.…”