Formation and Differentiation of Multiple Mesenchymal Lineages during Lung Development Is Regulated by β-catenin Signaling 英文参考文献.docVIP

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Formation and Differentiation of Multiple Mesenchymal Lineages during Lung Development Is Regulated by β-catenin Signaling 英文参考文献.doc

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Formation and Differentiation of Multiple Mesenchymal Lineages during Lung Development Is Regulated by β-catenin Signaling 英文参考文献

FormationandDifferentiationofMultipleMesenchymal LineagesduringLungDevelopmentIsRegulatedby b-cateninSignaling StijnP.DeLanghe1¤,GianniCarraro1,DeniseTefft1,ChanggongLi2,XinXu3,YangChai3,ParvizMinoo2,MohammadK.Hajihosseini4 ,Jacques Drouin5,VesaKaartinen1,Save′rioBellusci1* 1DevelopmentalBiologyProgram,DepartmentofSurgery,SabanResearchInstituteofChildrensHospitalLosAngeles,LosAngeles,California,United States of America, 2Department of Pediatrics, Women’s and Children’s Hospital, University of Southern California Keck School of Medicine, Los Angeles,California,UnitedStatesofAmerica,3CenterforCraniofacialMolecularBiology,SchoolofDentistry,UniversityofSouthernCalifornia,Los Angeles, California, United States of America, 4School of Biological Sciences, University of East Anglia (UEA), Norwich, Norfolk, United Kingdom, 5LaboratoiredeGe′ne′tiqueMole′culaire,InstitutdeRecherchesCliniquesdeMontre′al(IRCM),Montre′al,Que′bec, Canada Background. The role of ?-catenin signaling in mesodermal lineage formation and differentiation has been elusive. Cre/+ Methodology. To define the role of ?-catenin signaling in these processes, we used a Dermo1(Twist2) line to target a floxedb-cateninallele,throughouttheembryonicmesenchyme.Strikingly,theDermo1Cre/+;b-cateninf/2conditionalKnockOut embryos largely phenocopy Pitx12/2/Pitx22/2 double knockout embryos, suggesting that ?-catenin signaling in the mesenchyme depends mostly on the PITX family of transcription factors. We havedissected this relationship further in the developinglungsandfindthatmesenchymaldeletionofb-catenindifferentiallyaffectstwomajormesenchymallineages.The amplificationbutnotdifferentiationofFgf10-expressingparabronchialsmoothmuscleprogenitorcellsisdrasticallyreduced. In the angioblast-endothelial lineage, however, only differentiation into mature endothelial cells is impaired. Conclusion. Taken together these findings reveal a hierarchy of gene activity involving ?-catenin and PITX, as important regulators of