Spatial Bistability Generates hunchback Expression Sharpness in the Drosophila Embryo 英文参考文献.docVIP

SpatialBistabilityGenerateshunchbackExpression SharpnessintheDrosophilaEmbryo FranciscoJ.P.Lopes1,2,3*,FernandoM.C.Vieira3,4,DavidM.Holloway5,6,7,PauloM.Bisch3,AlexanderV. Spirov1,2 1Department of Applied Mathematics, Stony Brook University, Stony Brook, New York, United States of America, 2Center for Developmental Genetics, Stony Brook University,StonyBrook,NewYork,UnitedStatesofAmerica,3InstitutodeBiofisica,UniversidadeFederaldoRiodeJaneiro,RiodeJaneiro,Brazil,4InstitutodeQuimica, UniversidadedeBrasilia,Brasilia,Brazil,5MathematicsDepartment,BritishColumbiaInstituteofTechnology,Burnaby,BritishColumbia,Canada,6ChemistryDepartment, UniversityofBritishColumbia,Vancouver,BritishColumbia,Canada,7BiologyDepartment,UniversityofVictoria,Victoria,BritishColumbia,Canada Abstract Duringembryonicdevelopment,thepositionalinformationprovidedbyconcentrationgradientsofmaternalfactorsdirects patternformation by providing spatiallydependentcues for gene expression. In thefruit fly, Drosophila melanogaster ,a classic example of this is the sharp on–off activation of the hunchback (hb) gene at midembryo, in response to local concentrations of the smooth anterior–posterior Bicoid (Bcd) gradient. The regulatory region for hb contains multiple bindingsitesfortheBcdproteinaswellasmultiplebindingsitesfortheHbprotein.Somepreviousstudieshavesuggested thatBcdissufficientforproperlysharpenedHbexpression,yetotherevidencesuggestsaneedforadditionalregulation.We experimentally quantified the dynamics of hb gene expression in flies that were wild-type, were mutant for hb self- regulationorBcdbinding,orcontainedanartificialpromoterconstructconsistingofsixBcdandtwoHbsites.Inadditionto theseexperiments,wedevelopedareaction–diffusionmodelofhbtranscription,withBcdcooperativebindingandhbself- regulation, and used Zero Eigenvalue Analysis to look for multiple stationary states in the reaction network. Our model reproducesthehbdevelopmentaldynamicsandcorrectlypredictsthemutantpatterns.Analysisofourmode