2023
SMC5 Plays Independent Roles in Congenital Heart Disease and Neurodevelopmental Disability
O'Brien M, Pryzhkova M, Lake E, Mandino F, Shen X, Karnik R, Atkins A, Xu M, Ji W, Konstantino M, Brueckner M, Ment L, Khokha M, Jordan P. SMC5 Plays Independent Roles in Congenital Heart Disease and Neurodevelopmental Disability. International Journal Of Molecular Sciences 2023, 25: 430. PMID: 38203602, PMCID: PMC10779392, DOI: 10.3390/ijms25010430.Peer-Reviewed Original ResearchThe H2Bub1-deposition complex is required for human and mouse cardiogenesis
Barish S, Berg K, Drozd J, Berglund-Brown I, Khizir L, Wasson L, Seidman C, Seidman J, Chen S, Brueckner M. The H2Bub1-deposition complex is required for human and mouse cardiogenesis. Development 2023, 150: dev201899. PMID: 38038666, PMCID: PMC10730087, DOI: 10.1242/dev.201899.Peer-Reviewed Original ResearchInactivation of Invs/Nphp2 in renal epithelial cells drives infantile nephronophthisis like phenotypes in mouse
Li Y, Xu W, Makova S, Brueckner M, Sun Z. Inactivation of Invs/Nphp2 in renal epithelial cells drives infantile nephronophthisis like phenotypes in mouse. ELife 2023, 12: e82395. PMID: 36920028, PMCID: PMC10154023, DOI: 10.7554/elife.82395.Peer-Reviewed Original ResearchConceptsFlox/Valproic acidRenal fibrosisCyst formationEnd-stage renal diseaseMutant miceHistone deacetylase inhibitor valproic acidKidney function declineStage renal diseaseCell proliferationInhibitor valproic acidEpithelial-stromal crosstalkKnockout mouse modelRenal cyst formationCyst burdenRenal diseaseFunction declineInterstitial fibrosisDisease progressionStromal fibrosisTargeted therapyInfantile nephronophthisisMouse modelMyofibroblast activationRenal epithelial cellsCilia function as calcium-mediated mechanosensors that instruct left-right asymmetry
Djenoune L, Mahamdeh M, Truong T, Nguyen C, Fraser S, Brueckner M, Howard J, Yuan S. Cilia function as calcium-mediated mechanosensors that instruct left-right asymmetry. Science 2023, 379: 71-78. PMID: 36603098, PMCID: PMC9939240, DOI: 10.1126/science.abq7317.Peer-Reviewed Original Research
2022
Network assisted analysis of de novo variants using protein-protein interaction information identified 46 candidate genes for congenital heart disease
Xie Y, Jiang W, Dong W, Li H, Jin SC, Brueckner M, Zhao H. Network assisted analysis of de novo variants using protein-protein interaction information identified 46 candidate genes for congenital heart disease. PLOS Genetics 2022, 18: e1010252. PMID: 35671298, PMCID: PMC9205499, DOI: 10.1371/journal.pgen.1010252.Peer-Reviewed Original Research
2020
Genomic analyses implicate noncoding de novo variants in congenital heart disease
Richter F, Morton SU, Kim SW, Kitaygorodsky A, Wasson LK, Chen KM, Zhou J, Qi H, Patel N, DePalma SR, Parfenov M, Homsy J, Gorham JM, Manheimer KB, Velinder M, Farrell A, Marth G, Schadt EE, Kaltman JR, Newburger JW, Giardini A, Goldmuntz E, Brueckner M, Kim R, Porter GA, Bernstein D, Chung WK, Srivastava D, Tristani-Firouzi M, Troyanskaya OG, Dickel DE, Shen Y, Seidman JG, Seidman CE, Gelb BD. Genomic analyses implicate noncoding de novo variants in congenital heart disease. Nature Genetics 2020, 52: 769-777. PMID: 32601476, PMCID: PMC7415662, DOI: 10.1038/s41588-020-0652-z.Peer-Reviewed Original Research
2019
Histone H2B monoubiquitination regulates heart development via epigenetic control of cilia motility
Robson A, Makova SZ, Barish S, Zaidi S, Mehta S, Drozd J, Jin SC, Gelb BD, Seidman CE, Chung WK, Lifton RP, Khokha MK, Brueckner M. Histone H2B monoubiquitination regulates heart development via epigenetic control of cilia motility. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 14049-14054. PMID: 31235600, PMCID: PMC6628794, DOI: 10.1073/pnas.1808341116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCell ProliferationChromatin Assembly and DisassemblyCiliaDisease Models, AnimalEpigenesis, GeneticGene Expression Regulation, NeoplasticHeartHeart Defects, CongenitalHistonesHumansLoss of Function MutationMiceRegulatory Factor X Transcription FactorsSignal TransductionUbiquitinationUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesXenopusConceptsHistone H2B monoubiquitinationCilia genesH2B monoubiquitinationCilia motilityFunctional gene ontologyHuman congenital heart diseaseUpstream transcriptional regulatorsTissue-specific expressionChromatin remodeling genesChromatin remodelingEpigenetic controlH2Bub1 levelsTranscriptional regulatorsChIP-seqDepletion phenotypeGene OntologyGenomic analysisTranscription factorsKnockdown resultsLeft-right asymmetryCilia functionHeart developmentH2Bub1RNF20Complex consisting
2015
Intraciliary Calcium Oscillations Initiate Vertebrate Left-Right Asymmetry
Yuan S, Zhao L, Brueckner M, Sun Z. Intraciliary Calcium Oscillations Initiate Vertebrate Left-Right Asymmetry. Current Biology 2015, 25: 556-567. PMID: 25660539, PMCID: PMC4469357, DOI: 10.1016/j.cub.2014.12.051.Peer-Reviewed Original ResearchConceptsLeft-right organizerLR developmentCiliary motilityVertebrate left–right asymmetryLeft-right signalingLive zebrafish embryosVertebrate developmentLeft-right asymmetryZebrafish embryosSensory ciliaPolycystin-2Signaling cascadesMolecular signalsMolecular mechanismsIntraciliary calciumCation channelsMotilityBilateral symmetryCalcium sinkCiliaCalcium oscillationsPKD2SignalingEmbryosExtracellular fluidThe NIMA-like kinase Nek2 is a key switch balancing cilia biogenesis and resorption in the development of left-right asymmetry
Endicott SJ, Basu B, Khokha M, Brueckner M. The NIMA-like kinase Nek2 is a key switch balancing cilia biogenesis and resorption in the development of left-right asymmetry. Development 2015, 142: 4068-4079. PMID: 26493400, PMCID: PMC4712839, DOI: 10.1242/dev.126953.Peer-Reviewed Original ResearchAnimalsBody PatterningCentriolesCiliaGene Expression Regulation, DevelopmentalGene Knockdown TechniquesHistone Deacetylase 6Histone DeacetylasesHomeodomain ProteinsHumansIntercellular Signaling Peptides and ProteinsMiceMicroscopy, FluorescenceMutationNIMA-Related KinasesNuclear Pore Complex ProteinsProtein Serine-Threonine KinasesRNA InterferenceSignal TransductionTranscription FactorsXenopusXenopus Proteins
2003
Two Populations of Node Monocilia Initiate Left-Right Asymmetry in the Mouse
McGrath J, Somlo S, Makova S, Tian X, Brueckner M. Two Populations of Node Monocilia Initiate Left-Right Asymmetry in the Mouse. Cell 2003, 114: 61-73. PMID: 12859898, DOI: 10.1016/s0092-8674(03)00511-7.Peer-Reviewed Original Research
2002
Conserved function for embryonic nodal cilia
Essner JJ, Vogan KJ, Wagner MK, Tabin CJ, Yost HJ, Brueckner M. Conserved function for embryonic nodal cilia. Nature 2002, 418: 37-38. PMID: 12097899, DOI: 10.1038/418037a.Peer-Reviewed Original ResearchConceptsVertebrate body plan
2001
Cilia propel the embryo in the right direction
Brueckner M. Cilia propel the embryo in the right direction. American Journal Of Medical Genetics 2001, 101: 339-344. PMID: 11471157, DOI: 10.1002/1096-8628(20010715)101:4<339::aid-ajmg1442>3.0.co;2-p.Peer-Reviewed Original Research
2000
Molecular motors: the driving force behind mammalian left–right development
Supp D, Potter S, Brueckner M, Supp D, Potter S, Brueckner M. Molecular motors: the driving force behind mammalian left–right development. Trends In Cell Biology 2000, 10: 41-45. PMID: 10652513, DOI: 10.1016/s0962-8924(99)01701-8.Peer-Reviewed Original ResearchConceptsEarly vertebrate developmentMitotic spindle movementsLarge protein complexesLeft-right developmentLeft-right axisEmbryonic patterningVertebrate developmentProtein complexesCellular processesMicrotubule cytoskeletonVesicular transportSpindle movementsATP hydrolysisMolecular motorsDirectional movementCiliary beatingUnique roleCytoskeletonKinesinPatterningComplexesHydrolysisOf mice and men: Dissecting the genetic pathway that controls left‐right asymmetry in mice and humans
Schneider H, Brueckner M. Of mice and men: Dissecting the genetic pathway that controls left‐right asymmetry in mice and humans. American Journal Of Medical Genetics 2000, 97: 258-270. PMID: 11376437, DOI: 10.1002/1096-8628(200024)97:4<258::aid-ajmg1276>3.0.co;2-8.Peer-Reviewed Original ResearchMeSH KeywordsAbnormalities, MultipleAnimalsBody PatterningCiliaDyneinsEctodermEmbryonic and Fetal DevelopmentEndodermFetal ProteinsGastrulaGene Expression Regulation, DevelopmentalGenesGenes, HomeoboxGenes, LethalHomeodomain ProteinsHumansKinesinsMiceMice, Mutant StrainsMutationNotochordPhenotypeSpecies SpecificityTranscription FactorsConceptsLeft-right asymmetrySpontaneous mouse mutationGenetic pathwaysHuman homologueMouse mutationNode monociliaHuman mutationsHuman phenotypesFinal phenotypeOrchestrated mannerPathways resultsMouse phenotypeGenesLaterality determinationMutationsPhenotypeModel systemDifferent stepsMonociliaHomologuesCombination of analysisMicePathwayHuman developmentInitial asymmetry
1999
Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries
Supp D, Brueckner M, Kuehn M, Witte D, Lowe L, McGrath J, Corrales J, Potter S. Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries. Development 1999, 126: 5495-5504. PMID: 10556073, PMCID: PMC1797880, DOI: 10.1242/dev.126.23.5495.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAmino Acid SequenceAnimalsAxonemal DyneinsBinding SitesBody PatterningCatalytic DomainCiliaCloning, MolecularDyneinsFunctional LateralityGene Expression Regulation, DevelopmentalHeadMaleMiceMice, Inbred StrainsMolecular Sequence DataMutationNervous SystemSequence AnalysisSequence DeletionConceptsLeft-right dyneinLeft-right developmentLeft-right asymmetryEmbryonic day 8.0Microtubule-based motor proteinsAsymmetric expression patternLevel of sequenceComplete coding sequenceEmbryonic day 7.5Single amino acid differenceLeft-right specificationAmino acid differencesLeft-right axisLgl mutantsATP bindingConserved positionDay 8.0Inversus viscerum (iv) mouseCoding sequenceMotor proteinsDorsoventral axesExpression patternsGerm layersAcid differencesGenes
1998
Handed asymmetry in the mouse: Understanding how things go right (or left) by studying how they go wrong
Supp D, Brueckner M, Potter S. Handed asymmetry in the mouse: Understanding how things go right (or left) by studying how they go wrong. Seminars In Cell And Developmental Biology 1998, 9: 77-87. PMID: 9572117, DOI: 10.1006/scdb.1997.0186.Peer-Reviewed Original ResearchConceptsSevere morphological defectsAnalysis of genesAsymmetric expression patternLeft/right axisRight patterningGenetic pathwaysMouse mutationExpression patternsMorphological defectsDevelopmental asymmetryVertebratesImportance of regulationMutant micePattern formationRight axisGenesMutationsRegulationPathwayPatterningMiceDisruption
1997
Mutation of an axonemal dynein affects left–right asymmetry in inversus viscerum mice
Supp D, Witte D, Potter S, Brueckner M. Mutation of an axonemal dynein affects left–right asymmetry in inversus viscerum mice. Nature 1997, 389: 963-966. PMID: 9353118, PMCID: PMC1800588, DOI: 10.1038/40140.Peer-Reviewed Original ResearchConceptsAxonemal dynein heavy chain geneDynein heavy chain geneAsymmetric expression patternMicrotubule-based motorsEmbryonic day 7.5Vertebrate patterningLeft-right axisGenetic hierarchyLeft-right asymmetryEarly molecular mechanismsPositional cloningHeavy chain geneInversus viscerum (iv) mouseGene productsVisceral asymmetryAxonemal dyneinsSymmetrical embryosExpression patternsMolecular mechanismsLR determinationMolecular levelDay 7.5EmbryosLateralization defectsDynein
1996
The genetics of left-right development and heterotaxia
Bowers P, Brueckner M, Yost H. The genetics of left-right development and heterotaxia. Seminars In Perinatology 1996, 20: 577-588. PMID: 9090782, DOI: 10.1016/s0146-0005(96)80070-x.Peer-Reviewed Original ResearchConceptsLeft-right developmentMolecular genetic mechanismsPrimitive heart tubeSingle geneCardiac morphogenesisDifferent genesCardiac loopingHeart tubeGenesPhenotypeComplex groupHeterotaxiaMorphogenesisMost crucial stepCrucial stepGeneticsElucidationLoopingWide spectrumDevelopment resultsCongenital heart
1993
Left, right and without a cue
Howrich A, Brueckner M. Left, right and without a cue. Nature Genetics 1993, 5: 321-322. PMID: 8298636, DOI: 10.1038/ng1293-321.Peer-Reviewed Original Research
1992
Duplication/deficiency mapping of situs inversus viscerum (iv), a gene that determines left-right asymmetry in the mouse
McGrath J, Horwich A, Brueckner M. Duplication/deficiency mapping of situs inversus viscerum (iv), a gene that determines left-right asymmetry in the mouse. Genomics 1992, 14: 643-648. PMID: 1427890, DOI: 10.1016/s0888-7543(05)80163-6.Peer-Reviewed Original ResearchConceptsDistal mouse chromosome 12Distal chromosome 12Mouse chromosome 12Deficiency mappingChromosome 12Trisomic progenyLeft-right body axisGenetic map locationDerivative chromosomesLeft-right asymmetryDuplication analysisTelomeric regionsMap locationChromosomal regionsGene complexChromosome 5Recessive mutationsBody axisGenetic linkageNormal copyProximal regionProgenyChromosomesMutationsReciprocal translocation