Genetic Dissection of Differential Signaling Threshold Requirements for the Wntβ-Catenin Pathway In Vivo 英文参考文献.docVIP

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Genetic Dissection of Differential Signaling Threshold Requirements for the Wntβ-Catenin Pathway In Vivo 英文参考文献.doc

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Genetic Dissection of Differential Signaling Threshold Requirements for the Wntβ-Catenin Pathway In Vivo 英文参考文献

GeneticDissectionofDifferentialSignalingThreshold RequirementsfortheWnt/b-CateninPathwayInVivo MichaelBuchert1.,DimitrisAthineos2.,HelenE.Abud1,3,4.¤a,ZoeD.Burke5,MareeC.Faux1,MichaelS. Samuel1,2¤b,AndrewG.Jarnicki1,CatherineE.Winbanks6,IanP.Newton7,ValerieS.Meniel8 ,Hiromu Suzuki9,StevenA.Stacker1,InkeS.Na¨thke7,DavidTosh5,JoergHuelsken10,AlanR.Clarke8,JoanK. Heath1,OwenJ.Sansom2*,MatthiasErnst1* 1Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Australia, 2The Beatson Institute Cancer Research, Garscube Estate, Glasgow, United Kingdom,3DepartmentofAnatomyandCellBiology,UniversityofMelbourne,Melbourne,Australia, 4DepartmentofAnatomyandDevelopmental Biology,Monash University,Clayton,Australia,5CentreforRegenerativeMedicine,DepartmentofBiologyandBiochemistry,UniversityofBath,Bath,UnitedKingdom,6Departmentof Surgery, University of Melbourne, Parkville, Australia, 7Cell and Developmental Biology, University of Dundee, Dundee, United Kingdom, 8School of Biosciences, UniversityofCardiff,Cardiff,UnitedKingdom,9FirstDepartmentofInternalMedicine,SapporoMedicalUniversity,Sapporo,Japan,10EcolePolytechniqueFe′de′ralede Lausanne,SwissInstituteforExperimentalCancerResearch,Lausanne,Switzerland Abstract Contributions of null and hypomorphic alleles of Apc in mice produce both developmental and pathophysiological phenotypes.Toascribetheresultinggenotype-to-phenotyperelationshipunambiguouslytotheWnt/b-cateninpathway, we challenged the allele combinations by genetically restricting intracellular b-catenin expression in the corresponding compound mutant mice. Subsequent evaluation of the extent of resulting Tcf4-reporter activity in mouse embryo fibroblasts enabled genetic measurement of Wnt/b-catenin signaling in the form of an allelic series of mouse mutants. Different permissive Wntsignalingthresholds appear tobe requiredfortheembryonicdevelopment ofheadstructures, adult intestinal polyposis, hepatocellular carcinomas, liver zonation, and th