2024
A common allele increases endometrial Wnt4 expression, with antagonistic implications for pregnancy, reproductive cancers, and endometriosis
Pavličev M, McDonough-Goldstein C, Zupan A, Muglia L, Hu Y, Kong F, Monangi N, Dagdas G, Zupančič N, Maziarz J, Sinner D, Zhang G, Wagner G, Muglia L. A common allele increases endometrial Wnt4 expression, with antagonistic implications for pregnancy, reproductive cancers, and endometriosis. Nature Communications 2024, 15: 1152. PMID: 38346980, PMCID: PMC10861470, DOI: 10.1038/s41467-024-45338-4.Peer-Reviewed Original ResearchConceptsFrequency of deleterious allelesAssociated with multiple phenotypesResistance to invasionWnt4 locusAlpha binding sitesPleiotropic mutationsDeleterious allelesPleiotropic SNPsMouse genomeMultiple phenotypesWnt4 transcriptionPopulation frequencyMolecular mechanismsPreovulatory estrogen peakRs3820282Estrogen-responsive tissuesWnt4 expressionCRISPR/Cas 9AllelesTranscriptionEndometriotic fociEndometrial stromaMutationsEpithelial proliferationEstrogen peak
2021
Single-cell analysis of prostaglandin E2-induced human decidual cell in vitro differentiation: a minimal ancestral deciduogenic signal†
Stadtmauer DJ, Wagner G. Single-cell analysis of prostaglandin E2-induced human decidual cell in vitro differentiation: a minimal ancestral deciduogenic signal†. Biology Of Reproduction 2021, 106: 155-172. PMID: 34591094, PMCID: PMC8757638, DOI: 10.1093/biolre/ioab183.Peer-Reviewed Original ResearchMeSH KeywordsCell DifferentiationCell Line, TransformedCells, CulturedCyclic AMPCyclic AMP-Dependent Protein KinasesDeciduaDinoprostoneEndometriumFemaleFibroblastsGene ExpressionGenome-Wide Association StudyHumansMedroxyprogesterone AcetatePregnancyReceptors, Prostaglandin E, EP2 SubtypeSequence Analysis, RNASingle-Cell AnalysisConceptsPlacental mammalsCore gene regulatory networkCyclic AMP/protein kinase A (cAMP/PKA) pathwayProtein kinase A (PKA) pathwaySenescence-associated genesProgesterone-dependent activationGenome-wide studiesSingle-cell transcriptomicsGene regulatory networksProgesterone-dependent inductionMembrane-permeable cAMPKinase A PathwaySingle-cell analysisUse of PGE2Outgroup taxaCellular statesRegulatory networksPKA axisGene expressionDecidual genesPKA activationPGE2 receptor 2Progestin-dependent inductionA PathwayAdenylyl cyclase activation
2020
Transcriptomic responses to hypoxia in endometrial and decidual stromal cells
Rytkönen KT, Heinosalo T, Mahmoudian M, Ma X, Perheentupa A, Elo LL, Poutanen M, Wagner G. Transcriptomic responses to hypoxia in endometrial and decidual stromal cells. Reproduction 2020, 160: 39-51. PMID: 32272449, DOI: 10.1530/rep-19-0615.Peer-Reviewed Original ResearchConceptsDecidual stromal cellsEndometrial stromal fibroblastsEndometriotic stromal cellsStromal cellsInflammatory transcription factorsEpithelial-mesenchymal transitionExpression of JunDCEBP transcription factorsCell typesHealthy endometriumEndometriosis lesionsProgesterone receptorDecidualization processUterine endometriumStromal fibroblastsMesenchymal transitionProgesterone signalingEndometriumHypoxiaHypoxia pathwayTranscription factorsHuman reproductive successDistinct transcriptional statesExpression of genesJun/Fos
2015
The statistical geometry of transcriptome divergence in cell-type evolution and cancer
Liang C, Forrest A, Wagner G. The statistical geometry of transcriptome divergence in cell-type evolution and cancer. Nature Communications 2015, 6: 6066. PMID: 25585899, DOI: 10.1038/ncomms7066.Peer-Reviewed Original ResearchConceptsCell typesCell type modelCell type evolutionAncestral cell typeSister cell typesNovel cell typesGene expression profilesTranscriptome divergenceOrganismal complexityTranscriptomic dataExpression profilesCancer cell linesTranscriptomeCancer cellsCell linesNormal cellsKey predictionsStatistical geometryFANTOM5Statistical modelCellsEncodesTree structureLittle understandingDivergence
2008
Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals
Lynch VJ, Tanzer A, Wang Y, Leung FC, Gellersen B, Emera D, Wagner GP. Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 14928-14933. PMID: 18809929, PMCID: PMC2567470, DOI: 10.1073/pnas.0802355105.Peer-Reviewed Original ResearchConceptsCis-regulatory elementsHoxa-11Evolutionary changePlacental mammalsEutherian mammalsTranscription factorsCis-regulatory evolutionDirect regulatory targetsGene expression domainsStrong positive selectionNovel developmental pathwayPRL expressionTherian ancestorGene regulationExpression domainsPositive selectionRegulatory targetsNovel functionDevelopmental pathwaysMammalsSpatial expressionProlactin expressionGenesExpressionAdaptive changesThe gene regulatory logic of transcription factor evolution
Wagner GP, Lynch VJ. The gene regulatory logic of transcription factor evolution. Trends In Ecology & Evolution 2008, 23: 377-385. PMID: 18501470, DOI: 10.1016/j.tree.2008.03.006.Peer-Reviewed Original ResearchConceptsTranscription factor proteinsDevelopmental evolutionGene regulatory logicMinimal pleiotropic effectsTranscription factor evolutionFactor proteinTranscription factor functionEvolution of developmentTranscription factor genesCis-regulatory elementsFunction of proteinsAdaptive evolutionDevelopmental biologyRegulatory logicNovel functionFactor genesFactor functionProtein changesPleiotropic effectsProteinRecent studiesEvolutionGenesRelative contributionBiology
2007
The developmental genetics of homology
Wagner GP. The developmental genetics of homology. Nature Reviews Genetics 2007, 8: 473-479. PMID: 17486120, DOI: 10.1038/nrg2099.Peer-Reviewed Original ResearchA stochastic model for the evolution of transcription factor binding site abundance
Wagner GP, Otto W, Lynch V, Stadler PF. A stochastic model for the evolution of transcription factor binding site abundance. Journal Of Theoretical Biology 2007, 247: 544-553. PMID: 17475285, DOI: 10.1016/j.jtbi.2007.03.001.Peer-Reviewed Original Research
2004
Adaptive evolution of HoxA11 and HoxA13 at the origin of the uterus in mammals
Lynch V, Roth J, Takahashi K, Dunn C, Nonaka D, Stopper G, Wagner G. Adaptive evolution of HoxA11 and HoxA13 at the origin of the uterus in mammals. Proceedings Of The Royal Society B 2004, 271: 2201-2207. PMID: 15539344, PMCID: PMC1691855, DOI: 10.1098/rspb.2004.2848.Peer-Reviewed Original ResearchConceptsAdaptive evolutionTranscription factorsMolecular evolutionHoxa-11Hoxa-13Cis-regulatory evolutionAdaptive molecular evolutionEvolution of developmentMammalian female reproductive systemStrong positive selectionCis-regulatory elementsAmniote taxaDevelopmental genesStem lineageDevelopmental evolutionEvolutionary changeEutherian mammalsSpatial regulationPositive selectionMorphological charactersFemale reproductive organsGenesFemale reproductive systemReproductive organsMammals
2000
Evolution of Hoxa-11 in Lineages Phylogenetically Positioned along the Fin–Limb Transition
Chiu C, Nonaka D, Xue L, Amemiya C, Wagner G. Evolution of Hoxa-11 in Lineages Phylogenetically Positioned along the Fin–Limb Transition. Molecular Phylogenetics And Evolution 2000, 17: 305-316. PMID: 11083943, DOI: 10.1006/mpev.2000.0837.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SequenceAnimalsBinding SitesCell LineConserved SequenceDNAEvolution, MolecularExtremitiesFishesHeLa CellsHomeodomain ProteinsHumansIntronsMolecular Sequence DataPhylogenyProtein IsoformsSequence AlignmentSequence Analysis, DNASequence Homology, Amino AcidXenopusXenopus ProteinsZebrafishZebrafish ProteinsConceptsFin-limb transitionSequence evolutionAmino acid sequence comparisonsHoxa-11Domain IElectrophoretic mobility shift assaysMobility shift assaysAmino acid sequencePatterns of evolutionConsecutive alanine residuesWhole cell extractsEvolutionary timeAppendage developmentCharacter reconstructionEvolutionary changeTranscription factorsSequence comparisonIntron sequencesNucleotide conservationShift assaysAcid sequenceAlanine residuesLineagesAccelerated rateCoelacanthPopulation dependent Fourier decomposition of fitness landscapes over recombination spaces: Evolvability of complex characters
Stadler P, Seitz R, Wagner G. Population dependent Fourier decomposition of fitness landscapes over recombination spaces: Evolvability of complex characters. Bulletin Of Mathematical Biology 2000, 62: 399-428. PMID: 10812714, DOI: 10.1006/bulm.1999.0167.Peer-Reviewed Original ResearchHox cluster genomics in the horn shark, Heterodontus francisci
Kim C, Amemiya C, Bailey W, Kawasaki K, Mezey J, Miller W, Minoshima S, Shimizu N, Wagner G, Ruddle F. Hox cluster genomics in the horn shark, Heterodontus francisci. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 1655-1660. PMID: 10677514, PMCID: PMC26491, DOI: 10.1073/pnas.030539697.Peer-Reviewed Original ResearchConceptsHox gene clustersHox clustersHOXA clusterGene clusterHeterodontus francisciVertebrate body planHorn sharkGene-coding sequencesDivergence timesEvolutionary historyBody planHoxD clusterEvolutionary significanceSequence motifsVertebrate phylogenyDevelopmental processesGenetic entitiesStructural similarityControl motifsSharksCluster organizationMotifPhylogenyGenomicsNoncoding
1999
Evolution of Chordate Hox Gene Clustersa
RUDDLE F, AMEMIYA C, CARR J, KIM C, LEDJE C, SHASHIKANT C, WAGNER G. Evolution of Chordate Hox Gene Clustersa. Annals Of The New York Academy Of Sciences 1999, 870: 238-248. PMID: 10415487, DOI: 10.1111/j.1749-6632.1999.tb08884.x.Peer-Reviewed Original ResearchConceptsHox cluster duplicationsCluster duplicationBody plan evolutionTerms of genomeGene duplicationHox genesDevelopmental evolutionGene enhancerDuplication modelDuplicationVertebratesNew functionsChordatesInvertebratesGenomeImportant roleEvolutionUrogenital systemGenesEnhancerRoleDaughter clustersNeuromuscular interactionNovel features
1996
Evidence for Four Hox Clusters in the KillifishFundulus heteroclitus(Teleostei)
Misof B, Wagner G. Evidence for Four Hox Clusters in the KillifishFundulus heteroclitus(Teleostei). Molecular Phylogenetics And Evolution 1996, 5: 309-322. PMID: 8728389, DOI: 10.1006/mpev.1996.0026.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiological EvolutionDNA PrimersFishesGenes, HomeoboxHomeodomain ProteinsHumansKillifishesKineticsMiceModels, GeneticMolecular Sequence DataMultigene FamilyPhylogenyPolymerase Chain ReactionProbabilitySequence Homology, Amino AcidSequence Homology, Nucleic AcidConceptsHox clustersMammalian Hox genesTeleost Fundulus heteroclitusDiploid teleostsHox genesHomeobox sequencesPCR surveySequence comparisonLower vertebratesFundulus heteroclitusCognate groupsFirst evidenceSequenceOrthologsCluster AVertebratesTeleostsGenesNumber of representativesHeteroclitusClustersHumansMiceFragmentsRepresentatives