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The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster (2003)
| Citations: | 185 - 11 self |
BibTeX
@MISC{Albert03thetopology,
author = {Reka Albert and Hans G. Othmer},
title = {The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster},
year = {2003}
}
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Abstract
Expression of the Drosophila segment polarity genes is initiated by a prepattern 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 wildtype 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 analyze a Boolean model of this network which is based on a binary ON/OFF representation of transcription 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 over-expression 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 prepattern.
Keyphrases
regulatory interaction segment polarity gene drosophila melanogaster steady state expression pattern pair-rule gene product rate law wildtype expression pattern logical function detailed form wide range gene interaction over-expression experiment differential equation drosophila segment polarity gene embryonic development boolean model protein level functional detail gene expression kinetic parameter temporal pattern ectopic expression pattern various mutant wild type gene expression pattern several stage absolute level segment polarity gene network binary representation important insight crucial role
