dorsal/arxiv
View SchemaThe topology of the regulatory interactions predics the expression pattern of the segment polarity genes in Drosophila melanogaster
| Authors | Reka Albert, Hans G. Othmer |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0311019 |
| URL | https://arxiv.org/abs/q-bio/0311019 |
| Journal | Journal of Theoretical Biology 223, 1-18 (2003) |
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 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 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.
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"abstract": "Expression of the Drosophila segment polarity genes is initiated by a\nprepattern of pair-rule gene products and maintained by a network of regulatory\ninteractions throughout several stages of embryonic development. Analysis of a\nmodel of gene interactions based on differential equations showed that\nwild-type expression patterns of these genes can be obtained for a wide range\nof kinetic parameters, which suggests that the steady states are determined by\nthe topology of the network and the type of regulatory interactions between\ncomponents, not the detailed form of the rate laws. To investigate this, we\npropose and analyze a Boolean model of this network which is based on a binary\nON/OFF representation of transcription and protein levels, and in which the\ninteractions are formulated as logical functions. In this model the spatial and\ntemporal patterns of gene expression are determined by the topology of the\nnetwork and whether components are present or absent, rather than the absolute\nlevels of the mRNAs and proteins and the functional details of their\ninteractions. The model is able to reproduce the wild type gene expression\npatterns, as well as the ectopic expression patterns observed in\nover-expression experiments and various mutants. Furthermore, we compute\nexplicitly all steady states of the network and identify the basin of\nattraction of each steady state. The model gives important insights into the\nfunctioning of the segment polarity gene network, such as the crucial role of\nthe wingless and sloppy paired genes, and the network\u0027s ability to correct\nerrors in the prepattern.",
"arxiv_id": "q-bio/0311019",
"authors": [
"Reka Albert",
"Hans G. Othmer"
],
"categories": [
"q-bio.MN"
],
"journal_ref": "Journal of Theoretical Biology 223, 1-18 (2003)",
"title": "The topology of the regulatory interactions predics the expression pattern of the segment polarity genes in Drosophila melanogaster",
"url": "https://arxiv.org/abs/q-bio/0311019"
},
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