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dc.contributor.authorSoady, KJen_US
dc.contributor.authorTornillo, Gen_US
dc.contributor.authorKendrick, Hen_US
dc.contributor.authorMeniel, Ven_US
dc.contributor.authorOlijnyk-Dallis, Den_US
dc.contributor.authorMorris, JSen_US
dc.contributor.authorStein, Ten_US
dc.contributor.authorGusterson, BAen_US
dc.contributor.authorIsacke, CMen_US
dc.contributor.authorSmalley, MJen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2017-09-26T14:38:39Z
dc.date.issued2017-10-15en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28870991en_US
dc.identifierdev.149120en_US
dc.identifier.citationDevelopment, 2017, 144 (20), pp. 3777 - 3788en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/843
dc.identifier.eissn1477-9129en_US
dc.identifier.doi10.1242/dev.149120en_US
dc.description.abstractPTPRB is a transmembrane protein tyrosine phosphatase known to regulate blood vessel remodelling and angiogenesis. Here, we demonstrate that PTPRB negatively regulates branching morphogenesis in the mouse mammary epithelium. We show that Ptprb is highly expressed in adult mammary stem cells and also, although at lower levels, in oestrogen receptor-positive luminal cells. During mammary development, Ptprb expression is downregulated during puberty, a period of extensive ductal outgrowth and branching. In vivo shRNA knockdown of Ptprb in the cleared mammary fat pad transplant assay resulted in smaller epithelial outgrowths with an increased branching density and also increased branching in an in vitro organoid assay. Organoid branching was dependent on stimulation by FGF2, and Ptprb knockdown in mammary epithelial cells resulted in a higher level of fibroblast growth factor receptor (FGFR) activation and ERK1/2 phosphorylation, both at baseline and following FGF2 stimulation. Therefore, PTPRB regulates branching morphogenesis in the mammary epithelium by modulating the response of the FGFR signalling pathway to FGF stimulation. Considering the importance of branching morphogenesis in multiple taxa, our findings have general importance outside mammary developmental biology.en_US
dc.format.extent3777 - 3788en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectBranching morphogenesisen_US
dc.subjectFGFR2en_US
dc.subjectMammary stem cellsen_US
dc.subjectMouseen_US
dc.subjectPTPRBen_US
dc.subjectTerminal end bud gene expressionen_US
dc.subjectAnimalsen_US
dc.subjectBody Patterningen_US
dc.subjectEpithelial Cellsen_US
dc.subjectExtracellular Signal-Regulated MAP Kinasesen_US
dc.subjectFemaleen_US
dc.subjectFibroblast Growth Factor 2en_US
dc.subjectGene Expression Profilingen_US
dc.subjectGene Expression Regulation, Developmentalen_US
dc.subjectGreen Fluorescent Proteinsen_US
dc.subjectMammary Glands, Animalen_US
dc.subjectMiceen_US
dc.subjectMorphogenesisen_US
dc.subjectNeovascularization, Physiologicen_US
dc.subjectOligonucleotide Array Sequence Analysisen_US
dc.subjectOrganoidsen_US
dc.subjectPhosphorylationen_US
dc.subjectRNA, Small Interferingen_US
dc.subjectReceptor-Like Protein Tyrosine Phosphatases, Class 3en_US
dc.subjectReceptors, Estrogenen_US
dc.subjectReceptors, Fibroblast Growth Factoren_US
dc.subjectSignal Transductionen_US
dc.subjectStem Cellsen_US
dc.subjectTransgenesen_US
dc.titleThe receptor protein tyrosine phosphatase PTPRB negatively regulates FGF2-dependent branching morphogenesis.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-08-25en_US
rioxxterms.versionofrecord10.1242/dev.149120en_US
rioxxterms.licenseref.startdate2017-10-15en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfDevelopmenten_US
pubs.issue20en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology
pubs.publication-statusPublisheden_US
pubs.volume144en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMolecular Cell Biologyen_US
dc.contributor.icrauthorIsacke, Clareen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/