Cell-Sorting at the AP Boundary in the Drosophila Wing Primordium A Computational Model to Consolidate Observed Non-Local Effects of Hh Signaling 英文参考文献.docVIP

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Cell-Sorting at the AP Boundary in the Drosophila Wing Primordium A Computational Model to Consolidate Observed Non-Local Effects of Hh Signaling 英文参考文献.doc

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Cell-Sorting at the AP Boundary in the Drosophila Wing Primordium A Computational Model to Consolidate Observed Non-Local Effects of Hh Signaling 英文参考文献

Cell-SortingattheA/PBoundaryintheDrosophilaWing Primordium:AComputationalModeltoConsolidate ObservedNon-LocalEffectsofHhSignaling SabineSchilling1,2,MariaWillecke1,TinriAegerter-Wilmsen1,OlafA.Cirpka3,KonradBasler1 ,Christian vonMering1,2 * 1InstituteofMolecularLifeSciences,UniversityofZurich,Zurich,Switzerland,2SwissInstituteofBioinformatics,UniversityofZurich,Zurich,Switzerland,3Centerfor AppliedGeoscience,UniversityofTuebingen,Tuebingen,Germany Abstract Non-intermingling,adjacentpopulationsofcellsdefinecompartmentboundaries;suchboundariesareoftenessentialfor thepositioningandthemaintenanceoftissue-organizersduringgrowth.InthedevelopingwingprimordiumofDrosophila melanogaster, signaling by the secreted protein Hedgehog (Hh) is required for compartment boundary maintenance. However,theprecisemechanismofHhinputremainspoorlyunderstood.Here,wecombineexperimentalobservationsof perturbedHhsignalingwithcomputersimulationsofcellularbehavior,andconnectphysicalpropertiesofcellstotheirHh signalingstatus.WefindthatexperimentaldisruptionofHhsignalinghasobservableeffectsoncellsortingsurprisinglyfar fromthecompartmentboundary,whichisincontrasttoapreviousmodelthatconfinesHhinfluencetothecompartment boundary itself. We have recapitulated our experimental observations by simulations of Hh diffusion and transduction coupled to mechanical tension along cell-to-cell contact surfaces. Intriguingly, the best results were obtained under the assumptionthatHhsignalingcannotaltertheoveralltensionforceofthecell,butwillmerelyre-distributeitlocallyinside thecell,relativetothesignalingstatusofneighboringcells.Ourresultssuggestascenarioinwhichhomotypicinteractions ofaputativeHhtargetmoleculeatthecellsurfaceareconvertedintoamechanicalforce.Suchascenariocouldexplainwhy themechanicaloutputofHhsignalingappearstobeconfinedtothecompartmentboundary,despitethelongerrangeof theHhmoleculeitself.Ourstudyisthefirsttocoupleacellularvertexmodeldescribingmechanicalpropertiesofcellsina growing tissue, toan exp