A Role for Mesenchyme Dynamics in Mouse Lung Branching Morphogenesis 英文参考文献.docVIP

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A Role for Mesenchyme Dynamics in Mouse Lung Branching Morphogenesis 英文参考文献.doc

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A Role for Mesenchyme Dynamics in Mouse Lung Branching Morphogenesis 英文参考文献

ARoleforMesenchymeDynamicsinMouseLung BranchingMorphogenesis PierreBlanc1,2*,KarenCoste1,5,PierrePouchin3,Jean-MarcAza?¨s4,Lo?¨cBlanchon1,DenisGallot1,6, VincentSapin1,2 1Retinoids,DevelopmentandDevelopmentalDiseases–EA7281,MedicineSchool,AuvergneUniversity,Clermont-Ferrand,France,2DepartmentofBiochemistryand MolecularBiology,UniversityHospital,Clermont-Ferrand,France,3GReD,CNRS6247,INSERM1103,UMR,ClermontUniversity,Clermont-Ferrand,France,4Mathematic Institute, Toulouse III University, Toulouse, France, 5Department of Pediatrics, University Hospital, Clermont-Ferrand, France, 6Department of Obstetrics, University Hospital,Clermont-Ferrand,France Abstract Mammalianairwaysarehighlyramifiedtree-likestructuresthatdevelopbytherepetitivebranchingofthelungepithelium intothesurroundingmesenchymethroughreciprocalinteractions.Basedonamorphometricanalysisoftheepithelialtree, ithasbeenrecentlyproposedthatthecompletebranchingschemeisspecifiedearlyineachlineagebyaprogrammeusing elementarypatterningroutinesatspecificsitesandtimesinthedevelopinglung.However,thecoupleddynamicsofboth the epithelium and mesenchyme have been overlooked in this process. Using a qualitative and quantitative in vivo morphometric analysis of the E11.25 to E13.5 mouse whole right cranial lobe structure, we show that beyond the first generations,thebranchingstereotypyrelaxesandbothspatialandtemporalvariationsarecommon.Thebranchingpattern andbranchingratearesensitivetothedynamicchangesofthemesodermshapethatisinturnmainlydependentuponthe volume and shape of the surrounding intrathoracic organs. Spatial and temporal variations of the tree architecture are relatedtolocalandsubtlemodificationsofthemesodermgrowth.Remarkably,budsnevermeetaftersufferingbranching variations and continue to homogenously fill the opening spaces in the mesenchyme. Moreover despite inter-specimen variations,thegrowthoftheepithelialtreeandthemesenchymeremainshighlycorrelatedovertimeatthewholelobe level, implying a long-range regulation