A Multi-cell, Multi-scale Model of Vertebrate Segmentation and Somite Formation 英文参考文献.docVIP

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A Multi-cell, Multi-scale Model of Vertebrate Segmentation and Somite Formation 英文参考文献.doc

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A Multi-cell, Multi-scale Model of Vertebrate Segmentation and Somite Formation 英文参考文献

AMulti-cell,Multi-scaleModelofVertebrate SegmentationandSomiteFormation SusanD.Hester*,JulioM.Belmonte,J.ScottGens,SherryG.Clendenon,JamesA.Glazier BiocomplexityInstituteandDepartmentofPhysics,IndianaUniversityBloomington,Bloomington,Indiana,UnitedStatesofAmerica Abstract Somitogenesis,theformationofthebody’sprimarysegmentalstructurecommontoallvertebratedevelopment,requires coordinationbetweenbiologicalmechanismsatseveralscales.Explaininghowthesemechanismsinteractacrossscalesand how events are coordinated in space and time is necessary for a complete understanding of somitogenesis and its evolutionary flexibility. So far, mechanisms of somitogenesis have been studied independently. To test the consistency, integrabilityandcombinedexplanatorypowerofcurrentprevailinghypotheses,webuiltanintegratedclock-and-wavefront model including submodels of the intracellular segmentation clock, intercellular segmentation-clock coupling via Delta/ Notch signaling, an FGF8 determination front, delayed differentiation, clock-wavefront readout, and differential-cell-cell- adhesion-driven cell sorting. We identify inconsistencies between existing submodels and gaps in the current understandingofsomitogenesismechanisms,andproposenovelsubmodelsandextensionsofexistingsubmodelswhere necessary.Forreasonableinitialconditions,2Dsimulationsofourmodelrobustlygeneratespatiallyandtemporallyregular somites,realisticdynamicmorphologiesandspontaneousemergenceofanterior-travelingstripesofLfng.Weshowthat these traveling stripes arepseudo-waves rather thantrue propagating waves. Our model is flexible enough to generate interspecies-likevariationinsomitesizeinresponsetochangesinthePSMgrowthrateandsegmentation-clockperiod,and inthenumberandwidthofLfngstripesinresponsetochangesinthePSMgrowthrate,segmentation-clockperiodand PSMlength. Citation: Hester SD, Belmonte JM, Gens JS, Clendenon SG, Glazier JA (2011) A Multi-cell, Multi-scale Model of Vertebrate Segmentation and Somite Formation.PLoSComputBiol7(