Gene Circuit Analysis of the Terminal Gap Gene huckebein 英文参考文献.docVIP

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Gene Circuit Analysis of the Terminal Gap Gene huckebein 英文参考文献.doc

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Gene Circuit Analysis of the Terminal Gap Gene huckebein 英文参考文献

GeneCircuitAnalysisoftheTerminalGapGene huckebein MaksatAshyraliyev1,KenSiggens2,HildeJanssens3,JokeBlom1,MichaelAkam2,JohannesJaeger2,3* 1Center for Mathematics and Computer Science, Centrum Wiskunde and Informatica, Amsterdam, The Netherlands, 2Laboratory for Development and Evolution, University Museum of Zoology, Department of Zoology, University of Cambridge, Cambridge, United Kingdom, 3EMBL/CRG Research Unit in Systems Biology, CRG– CentredeRegulacio′ Geno`mica,UniversitatPompeuFabra,Barcelona,Spain Abstract The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation.Thegapgenenetworkconstitutesthefirstzygoticregulatorytierinthehierarchyofthesegmentationgenes involvedinspecifyingthepositionofbodysegments.Here,weuseanintegrative,systems-levelapproachtoinvestigatethe regulatoryeffectoftheterminalgapgenehuckebein(hkb)ongapgeneexpression.Wepresentquantitativeexpressiondata fortheHkbprotein,whichenableustoincludehkbingapgenecircuitmodels.Gapgenecircuitsaremathematicalmodels of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achievedbyfittingthemodeltogapgeneexpressionpatterns,inordertoobtainestimatesforregulatoryparameterswhich predictaspecificnetworktopology.Weshowhowconsideringvariabilityinthedatacombinedwithanalysisofparameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second,gapgenecircuitspresentedhereareabletoreproducemutantsofterminalgapgenes,whilepreviouslypublished modelswereunabletoreproduceanynullm