Simulating the Mammalian Blastocyst - Molecular and Mechanical Interactions Pattern the Embryo 英文参考文献.docVIP

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Simulating the Mammalian Blastocyst - Molecular and Mechanical Interactions Pattern the Embryo 英文参考文献.doc

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Simulating the Mammalian Blastocyst - Molecular and Mechanical Interactions Pattern the Embryo 英文参考文献

SimulatingtheMammalianBlastocyst-Molecularand MechanicalInteractionsPatterntheEmbryo PawelKrupinski1,VijayChickarmane2,CarstenPeterson1,3* 1ComputationalBiologyBiologicalPhysics,DepartmentofAstronomyandTheoreticalPhysics,LundUniversity,Lund,Sweden,2DivisionofBiology,CaliforniaInstitute ofTechnology,Pasadena,California,UnitedStatesofAmerica,3LundStrategicResearchCenterforStemCellBiologyandCellTherapy,LundUniversity,Lund,Sweden Abstract Mammalianembryogenesisisadynamicprocessinvolvinggeneexpressionandmechanicalforcesbetweenproliferating cells.Theexactnatureoftheseinteractions,whichdeterminethelineagepatterningofthetrophectodermandendoderm tissuesoccurringinahighlyregulatedmanneratpreciseperiodsduringtheembryonicdevelopment,isanareaofdebate. We have developed a computational modeling framework for studying this process, by which the combined effects of mechanicalandgeneticinteractionsareanalyzedwithinthecontextofproliferatingcells.Atapurelymechanicallevel,we demonstrate that the perpendicular alignment of the animal-vegetal (a-v) and embryonic-abembryonic (eb-ab) axes is a resultofminimizingthetotalelasticconformationalenergyoftheentirecollectionofcells,whichareconstrainedbythe zonapellucida.Thecouplingofgeneexpressionwiththemechanicsofcellmovementisimportantforformationofboth the trophectoderm and the endoderm. In studying the formation of the trophectoderm, we contrast and compare quantitativelytwohypotheses:(1)Thepositiondeterminesgeneexpression,and(2)thegeneexpressiondeterminesthe position.Ourmodel,whichcouplesgeneexpressionwithmechanics,suggeststhatdifferentialadhesionbetweendifferent cell types is a critical determinant in the robust endoderm formation. In addition to differential adhesion, two different testablehypothesesemergewhenconsideringendodermformation:(1)Adirectionalforceactsoncertaincellsandmoves themintoformingtheendodermlayer,whichseparatestheblastocoelandthecellsoftheinnercellmass(ICM).Inthiscase theblastocoelsimplyactsasastaticboundary.(2)Theblast