2014
Deletion of the Nuclear Localization Sequences and C-Terminus of PTHrP Impairs Embryonic Mammary Development but also Inhibits PTHrP Production
Boras-Granic K, Dann P, VanHouten J, Karaplis A, Wysolmerski J. Deletion of the Nuclear Localization Sequences and C-Terminus of PTHrP Impairs Embryonic Mammary Development but also Inhibits PTHrP Production. PLOS ONE 2014, 9: e90418. PMID: 24785493, PMCID: PMC4006745, DOI: 10.1371/journal.pone.0090418.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersFemaleGene DeletionGene Expression Regulation, DevelopmentalMammary Glands, AnimalMiceMice, TransgenicNuclear Localization SignalsParathyroid Hormone-Related ProteinPeptide FragmentsProtein Interaction Domains and MotifsSex CharacteristicsConceptsMammary gland developmentType 1 PTH/PTHrP receptorC-terminusEmbryonic mammary gland developmentPTH/PTHrP receptorGland developmentPTHrP mRNA levelsNuclear localization signalNuclear localization sequenceHormone-related proteinEmbryonic mammary developmentMammary epithelial cellsLocalization signalNuclear functionsPTHrP productionPTHrP receptorAlternative animal modelLocalization sequencePTHR1 geneAnimal modelsEndocrine fashionMutant formsPTHrPDevelopmental defectsMesenchyme differentiation
2012
Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme
Hiremath M, Dann P, Fischer J, Butterworth D, Boras-Granic K, Hens J, Van Houten J, Shi W, Wysolmerski J. Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme. Development 2012, 139: 4239-4249. PMID: 23034629, PMCID: PMC3478689, DOI: 10.1242/dev.080671.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninCell DifferentiationFemaleGene Expression Regulation, DevelopmentalKeratinocytesLymphoid Enhancer-Binding Factor 1Mammary Glands, AnimalMesodermMiceMice, KnockoutParathyroid Hormone-Related ProteinReceptors, Parathyroid HormoneThrombospondinsWnt ProteinsWnt Signaling PathwayConceptsLoss of PTHrPOverexpression of PTHrPHormone-related proteinMammary mesenchymeΒ-cateninEmbryonic mammary mesenchymeWnt pathwayWnt/β-cateninEmbryonic mammary developmentCanonical Wnt pathwayPTHrPMammary developmentMammary budAbnormal differentiationReduced expressionBasal keratinocytesVentral skinReporter activityBud cellsMarkersCanonical WntInappropriate differentiationAbolished expressionMesenchyme markersOverexpression
2011
Skeletal recovery after weaning does not require PTHrP*
Kirby BJ, Ardeshirpour L, Woodrow JP, Wysolmerski JJ, Sims NA, Karaplis AC, Kovacs CS. Skeletal recovery after weaning does not require PTHrP*. Journal Of Bone And Mineral Research 2011, 26: 1242-1251. PMID: 21308774, PMCID: PMC3179289, DOI: 10.1002/jbmr.339.Peer-Reviewed Original ResearchConceptsBone mineral contentParathyroid hormoneBone massSerum calciumLumbar spine bone mineral contentTrabecular bone mineral contentParathyroid hormone-related proteinSpine bone mineral contentBone formationNormal serum calciumLow bone massAdult bone massPTHrP mRNA expressionWild-type miceHormone-related proteinEnd of lactationType 1 collagenUrine calciumSkeletal recoveryPTHrP mRNANull miceMRNA expressionFull recoveryMiceConditional knockout
2010
Molecular Mechanisms Guiding Embryonic Mammary Gland Development
Cowin P, Wysolmerski J. Molecular Mechanisms Guiding Embryonic Mammary Gland Development. Cold Spring Harbor Perspectives In Biology 2010, 2: a003251. PMID: 20484386, PMCID: PMC2869520, DOI: 10.1101/cshperspect.a003251.BooksMeSH KeywordsAnimalsCell LineageFemaleGene Expression Regulation, DevelopmentalMammary Glands, AnimalConceptsMammary glandMammary gland developmentBreast cancerEmbryonic mammary developmentBreast developmentEmbryonic mammary gland developmentMammary developmentRegulation of morphogenesisGland developmentMolecular pathwaysPregnancySubsequent developmentDuct systemSexual maturationMolecular mechanismsGlandPotential relevanceSurface ectodermEpidermal appendagesPathophysiologyCancer
2009
Analysis of gene expression in PTHrP−/− mammary buds supports a role for BMP signaling and MMP2 in the initiation of ductal morphogenesis
Hens J, Dann P, Hiremath M, Pan T, Chodosh L, Wysolmerski J. Analysis of gene expression in PTHrP−/− mammary buds supports a role for BMP signaling and MMP2 in the initiation of ductal morphogenesis. Developmental Dynamics 2009, 238: 2713-2724. PMID: 19795511, PMCID: PMC2862621, DOI: 10.1002/dvdy.22097.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 4Cells, CulturedDipeptidesDown-RegulationGene Expression Regulation, DevelopmentalHydroxamic AcidsIntercellular Signaling Peptides and ProteinsKeratinsMammary Glands, AnimalMatrix Metalloproteinase 2Matrix Metalloproteinase InhibitorsMesodermMiceMice, KnockoutMorphogenesisOligonucleotide Array Sequence AnalysisParathyroid Hormone-Related ProteinProtease InhibitorsSignal TransductionTranscription FactorsUp-RegulationConceptsGene expressionMammary budMammary mesenchymeDuctal outgrowthMesenchymal cellsEmbryonic mammary developmentMMP2 gene expressionEmbryonic mammary budFunctional roleGenesDuctal morphogenesisBud culturesMammary developmentBudsPTHrP effectsBMPMesenchymeExpressionMMP2 activityMMP2OutgrowthVentral skinCellsMorphogenesisBMP4
2007
BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction
Hens JR, Dann P, Zhang JP, Harris S, Robinson GW, Wysolmerski J. BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction. Development 2007, 134: 1221-1230. PMID: 17301089, DOI: 10.1242/dev.000182.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 4Bone Morphogenetic Protein Receptors, Type IBone Morphogenetic ProteinsDNA-Binding ProteinsEmbryo, MammalianGene Expression Regulation, DevelopmentalHair FollicleHomeodomain ProteinsMammary Glands, AnimalMesodermMiceMice, Mutant StrainsParathyroid Hormone-Related ProteinRNA, MessengerSignal TransductionUp-RegulationConceptsMammary mesenchymeBMP signalingMammary budMesenchymal cellsMammary epithelial cell fateEpithelial cell fateParathyroid hormone-related proteinHair follicle inductionEmbryonic mammary developmentMammary bud formationHormone-related proteinHair follicle formationMammary epithelial cellsMsx2 gene expressionCell fateEmbryonic epidermisMsx2 geneMsx2 expressionMammary placodesMouse embryosGene expressionVentral epidermisDuctal developmentBMP4Bud formation
2004
Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis
Chu EY, Hens J, Andl T, Kairo A, Yamaguchi TP, Brisken C, Glick A, Wysolmerski JJ, Millar SE. Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development 2004, 131: 4819-4829. PMID: 15342465, DOI: 10.1242/dev.01347.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene Expression Regulation, DevelopmentalIntercellular Signaling Peptides and ProteinsMammary Glands, AnimalMiceMice, KnockoutMice, TransgenicMorphogenesisProteinsProto-Oncogene ProteinsSignal TransductionWnt ProteinsWnt-5a ProteinConceptsMammary gland morphogenesisPlacode developmentGland morphogenesisCanonical WntEmbryonic mammary developmentMammary placode formationHair follicle formationSkin appendage morphogenesisWnt pathway activityAdditional WntAppendage morphogenesisWnt signalsPlacode formationWnt genesMolecular controlMammary morphogenesisMammary placodesUnderlying mesenchymeMorphogenesisWnt pathwayWntPathway activityWnt inhibitor Dickkopf-1PlacodeElevated expression
2001
Temporally regulated overexpression of parathyroid hormone-related protein in the mammary gland reveals distinct fetal and pubertal phenotypes
Dunbar ME, Dann P, Brown CW, Van Houton J, Dreyer B, Philbrick WP, Wysolmerski JJ. Temporally regulated overexpression of parathyroid hormone-related protein in the mammary gland reveals distinct fetal and pubertal phenotypes. Journal Of Endocrinology 2001, 171: 403-416. PMID: 11739006, DOI: 10.1677/joe.0.1710403.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell DivisionEmbryonic and Fetal DevelopmentFemaleGene Expression Regulation, DevelopmentalMammary Glands, AnimalMiceMice, TransgenicMorphogenesisParathyroid Hormone-Related ProteinPhenotypeProteinsTetracyclineConceptsParathyroid hormone-related proteinHormone-related proteinPTHrP overexpressionMammary glandLobuloalveolar developmentDuctal elongationMammary developmentOverexpression of PTHrPDouble transgenic miceTransgenic mice resultsTerminal end budsEpithelial cell apoptosisPubertal phenotypesDuctal branchingEmbryonic mammary developmentTransgenic miceMice resultsPTHrPEnd budsDecrease apoptosisCell apoptosisBasal rateDuctal morphogenesisCell proliferationDuctal treeParathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development
Foley J, Dann P, Hong J, Cosgrove J, Dreyer B, Rimm D, Dunbar M, Philbrick W, Wysolmerski J. Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development. Development 2001, 128: 513-525. PMID: 11171335, DOI: 10.1242/dev.128.4.513.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninCell DifferentiationCell LineageCytoskeletal ProteinsDNA-Binding ProteinsEpidermal CellsEpidermisEpithelial CellsFemaleGene Expression Regulation, DevelopmentalHistocytochemistryLymphoid Enhancer-Binding Factor 1Mammary Glands, AnimalMiceMice, KnockoutMice, TransgenicModels, BiologicalNipplesParathyroid Hormone-Related ProteinProteinsReceptor, Parathyroid Hormone, Type 1Receptors, Parathyroid HormoneSignal TransductionTrans-ActivatorsTranscription FactorsTransgenesConceptsPTH/PTHrP receptorCell fateHormone-related proteinMammary epithelial cell fateMammary mesenchymeCell fate decisionsEpithelial cell fatePTHrP receptorEmbryonic mammary glandMesenchymal cellsType I PTH/PTHrP receptorEmbryonic mammary developmentMammary epithelial cellsParathyroid hormone-related proteinEpithelial cellsEpithelial fateEpidermal fateFate decisionsEpithelial morphogenesisAbsence of PTHrPMesenchymal expressionVentral epidermisProper developmentSkin differentiationCombination of lossMammary ductal and alveolar development: Lesson learned from genetically manipulated mice
Dunbar M, Wysolmerski J. Mammary ductal and alveolar development: Lesson learned from genetically manipulated mice. Microscopy Research And Technique 2001, 52: 163-170. PMID: 11169864, DOI: 10.1002/1097-0029(20010115)52:2<163::aid-jemt1002>3.0.co;2-r.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene Expression Regulation, DevelopmentalMammary Glands, AnimalMiceMice, KnockoutMice, TransgenicConceptsMammary developmentMammary gland developmentDevelopmental biologistsMouse genomeMammary glandCertain genesKnockout technologyMolecular mechanismsGland developmentDuctal developmentFundamental processesAlveolar developmentGenomeRecent advancesMouse modelGenesMechanismBiologistsTransgenicDifferentiationIntensive effortsMoleculesExpressionGlandDevelopment
1999
Parathyroid hormone-related protein signaling is necessary for sexual dimorphism during embryonic mammary development
Dunbar M, Dann P, Robinson G, Hennighausen L, Zhang J, Wysolmerski J. Parathyroid hormone-related protein signaling is necessary for sexual dimorphism during embryonic mammary development. Development 1999, 126: 3485-3493. PMID: 10409496, DOI: 10.1242/dev.126.16.3485.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedApoptosisEpithelial CellsFemaleGene Expression Regulation, DevelopmentalHeterozygoteMaleMammary Glands, AnimalMesodermMiceMice, KnockoutParathyroid Hormone-Related ProteinProteinsReceptor, Parathyroid Hormone, Type 1Receptors, AndrogenReceptors, Parathyroid HormoneSex CharacteristicsTenascinConceptsAndrogen receptorMammary mesenchymeMammary budPTH/PTHrP receptorParathyroid hormone-related proteinHormone-related proteinEpithelial budsAR expressionPTHrP expressionMale micePTHrP receptorEmbryonic mammary developmentMammary epithelial cellsEpithelial-mesenchymal signalingMammary developmentTransgenic overexpressionMammary glandBasal epidermisEpithelial cellsC expressionTenascin CVentral dermisReceptorsAndrogensPTHrP
1998
Stromal Cells Are Critical Targets in the Regulation of Mammary Ductal Morphogenesis by Parathyroid Hormone-Related Protein
Dunbar M, Young P, Zhang J, McCaughern-Carucci J, Lanske B, Orloff J, Karaplis A, Cunha G, Wysolmerski J. Stromal Cells Are Critical Targets in the Regulation of Mammary Ductal Morphogenesis by Parathyroid Hormone-Related Protein. Developmental Biology 1998, 203: 75-89. PMID: 9806774, DOI: 10.1006/dbio.1998.9029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding, CompetitiveCyclic AMPEmbryonic and Fetal DevelopmentEpitheliumFemaleGene Expression Regulation, DevelopmentalIn Situ HybridizationMammary Glands, AnimalMesodermMiceMice, Inbred StrainsMorphogenesisParathyroid Hormone-Related ProteinProteinsReceptors, Parathyroid HormoneRNA, MessengerStromal CellsConceptsPTH/PTHrP receptorPTHrP receptorStromal cellsMammary epithelial cell morphogenesisMammary developmentEpithelial cell morphogenesisMammary glandAmino-terminal PTHrPEpithelial cellsHormone-related proteinMammary ductal morphogenesisMammary epithelial cellsCritical targetMammary stromal cellsDuctal branching morphogenesisDevelopmental regulatory moleculeStromal cell functionMurine mammary glandCell morphogenesisMammary morphogenesisHumoral hypercalcemiaParathyroid hormoneTumor productsRegulatory moleculesMammary mesenchymeRescue of the parathyroid hormone-related protein knockout mouse demonstrates that parathyroid hormone-related protein is essential for mammary gland development
Wysolmerski J, Philbrick W, Dunbar M, Lanske B, Kronenberg H, Karaplis A, Broadus A. Rescue of the parathyroid hormone-related protein knockout mouse demonstrates that parathyroid hormone-related protein is essential for mammary gland development. Development 1998, 125: 1285-1294. PMID: 9477327, DOI: 10.1242/dev.125.7.1285.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedGene DeletionGene Expression Regulation, DevelopmentalGene Transfer TechniquesImmunohistochemistryIn Situ HybridizationMammary Glands, AnimalMiceMice, KnockoutMorphogenesisParathyroid Hormone-Related ProteinPhenotypeProteinsReceptors, Parathyroid HormoneRNA, MessengerConceptsHormone-related proteinMammary epithelial cellsMammary gland developmentEpithelial cellsPTH/PTHrP receptor expressionPTH/PTHrP receptorParathyroid hormone-related proteinMammary glandPTH/PTHrP receptor geneAmino-terminal PTHrPMammary duct systemPTHrP-knockout miceMammary mesenchymeOverexpression of PTHrPGland developmentPTHrP receptor expressionProtein knockout miceAbsence of PTHrPSitu hybridization histochemistryAbility of PTHrPTransgenic expressionEpithelial-mesenchymal communicationNeonatal deathHumoral hypercalcemiaEarly pregnancy