Stabilizing patterning in the Drosophila segment polarity network by selecting models in silico

Bio Systems
Gautier StollFelix Naef

Abstract

The segmentation of Drosophila is a prime model to study spatial patterning during embryogenesis. The spatial expression of segment polarity genes results from a complex network of interacting proteins whose expression products are maintained after successful segmentation. This prompted us to investigate the stability and robustness of this process using a dynamical model for the segmentation network based on Boolean states. The model consists of intra-cellular as well as inter-cellular interactions between adjacent cells in one spatial dimension. We quantify the robustness of the dynamical segmentation process by a systematic analysis of mutations. Our starting point consists in a previous Boolean model for Drosophila segmentation. We define mathematically the notion of dynamical robustness and show that the proposed model exhibits limited robustness in gene expression under perturbations. We applied in silico evolution (mutation and selection) and discover two classes of modified gene networks that have a more robust spatial expression pattern. We verified that the enhanced robustness of the two new models is maintained in differential equations models. By comparing the predicted model with experiments on mutated flies, we th...Continue Reading

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Citations

Jun 23, 2012·Circulation Research·Erzsébet Ravasz Regan, William C Aird
Aug 31, 2012·BMC Systems Biology·Gautier StollLaurence Calzone
Nov 13, 2012·Methods : a Companion to Methods in Enzymology·Assieh Saadatpour, Réka Albert
Nov 26, 2010·Clinical Chemistry and Laboratory Medicine : CCLM·Tadej Pajič

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