The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster.

By Réka Albert, Hans G. Othmer. Journal of Theoretical Biology, 2003

987 citations recorded by the source corpus.

Expression of the Drosophila segment polarity genes is initiated by a pre-pattern of pair-rule gene products and maintained by a network of regulatory interactions throughout several stages of embryonic development. Analysis of a model of gene interactions based on differential equations showed that wild-type expression patterns of these genes can be obtained for a wide range of kinetic parameters, which suggests that the steady states are determined by the topology of the network and the type of regulatory interactions between components, not the detailed form of the rate laws. To investigate this, we propose and analyse a Boolean model of this network which is based on a binary ON/OFF representation of mRNA and protein levels, and in which the interactions are formulated as logical functions. In this model the spatial and temporal patterns of gene expression are determined by the topology of the network and whether components are present or absent, rather than the absolute levels of the mRNAs and proteins and the functional details of their interactions. The model is able to reproduce the wild-type gene expression patterns, as well as the ectopic expression patterns observed in overexpression experiments and various mutants. Furthermore, we compute explicitly all steady states of the network and identify the basin of attraction of each steady state. The model gives important insights into the functioning of the segment polarity gene network, such as the crucial role of the wingless and sloppy paired genes, and the network's ability to correct errors in the pre-pattern.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e1315b882badbd2d95ff30fd75372a04798a1f2b

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Citations in the corpus

Robustness: mechanisms and consequences (2009, background): “The vulval network has been modeled in this way [57], as have different levels of the segmentation hierarchy in Drosophila [58–60].”
Executable cell biology (2007, background): “Boolean networks have proved useful in analyzing system dynamics and reasoning about the stability and robustness of biological systems 34,35 .”
A computational algebra approach to the reverse engineering of gene regulatory networks. (2003, methodology): “Figure 1 depicts the graph of connections in the Boolean model in (Albert and Othmer, 2003).”
Scale-free networks in cell biology (2005, background): “Indeed, increasing evidence indicates the crucial role of network topology in determining dynamic behavior and function and robustness to fluctuations in kinetic parameters (Albert and Othmer, 2003; Barkai and Leibler, 1997; Chaves et al., 2005; Li, F. et al., 2004; von Dassow et al., 2000).”
Colloquium: Criticality and dynamical scaling in living systems (2017, background): “…RBN models running on top of such networks –with the empirically-determined architecture of diverse organisms such as S. cerevisiae and E. coli (Albert and Othmer, 2003)– it was concluded that they all are indeed very close to criticality, in the sense of marginal propagation of perturbations…”
Robustness Can Evolve Gradually in Complex Regulatory Gene Networks with Varying Topology (2007, result): “play a central role; this is in contrast with most studies determining the generic properties of random Boolean networks [”
Network biology: understanding the cell's functional organization (2004, background): “The development of the correct segment polarity pattern in Drosophila melanogaster embryos is also robust to marked changes in the initial conditions, reaction parameters, or to the absence of certain gene product”
Controllability of Boolean control networks via the Perron-Frobenius theory (2012, background): “(2003)); the network controlling the segment polarity genes in the fly Drosophila melanogaster (Albert and Othmer (2003); Chaves et al. (2005)); the ABC network determining floral organ cell fate in Arabidopsis (Espinosa-Soto et al. (2004); Chaos et al. (2006)).”