The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster.
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.
Albert
Réka
R
School of Mathematics, University of Minnesota, 127 Vincent Hall, Minneapolis, MN 55455, USA. ralbert@math.umn.edu
Othmer
Hans G
HG
D000818:Animals; D001798:Blood Proteins / Q000235:genetics; D002970:Cleavage Stage, Ovum / Q000502:physiology*; D003181:Complement C4; D003198:Computer Simulation; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D017344:Genes, Insect; D005809:Genes, Regulator; D008565:Membrane Proteins / Q000235:genetics; D008957:Models, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011956:Receptors, Cell Surface; D051155:Wnt1 Protein
D001798:Blood Proteins; C018386:C4a protein, mouse; D003181:Complement C4; D029721:Drosophila Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D051155:Wnt1 Protein; C070844:ptc protein, Drosophila; C074622:wg protein, Drosophila