2017
Disruptions in asymmetric centrosome inheritance and WDR62-Aurora kinase B interactions in primary microcephaly
Sgourdou P, Mishra-Gorur K, Saotome I, Henagariu O, Tuysuz B, Campos C, Ishigame K, Giannikou K, Quon JL, Sestan N, Caglayan AO, Gunel M, Louvi A. Disruptions in asymmetric centrosome inheritance and WDR62-Aurora kinase B interactions in primary microcephaly. Scientific Reports 2017, 7: 43708. PMID: 28272472, PMCID: PMC5341122, DOI: 10.1038/srep43708.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAurora Kinase BBrainCell CycleCell Cycle ProteinsCell DifferentiationCell ProliferationCentrosomeConsanguinityDisease Models, AnimalEpistasis, GeneticFluorescent Antibody TechniqueGene ExpressionHumansInheritance PatternsMaleMiceMice, KnockoutMicrocephalyMutationNerve Tissue ProteinsNeural Stem CellsPedigreeWhole Genome SequencingConceptsChromosome passenger complexPatient-derived fibroblastsCentrosome inheritanceNeocortical progenitorsDisease-associated mutant formsSpindle pole localizationAurora kinase BPassenger complexMitotic progressionMouse orthologDiverse functionsMutant formsWD repeat domain 62Key regulatorCPC componentsKinase BPole localizationPrimary microcephalyLate neurogenesisRecessive mutationsNeuronal differentiationWDR62Severe brain malformationsReduced proliferationNeocortical development
2014
Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors
Mishra-Gorur K, Çağlayan AO, Schaffer AE, Chabu C, Henegariu O, Vonhoff F, Akgümüş GT, Nishimura S, Han W, Tu S, Baran B, Gümüş H, Dilber C, Zaki MS, Hossni HA, Rivière JB, Kayserili H, Spencer EG, Rosti RÖ, Schroth J, Per H, Çağlar C, Çağlar Ç, Dölen D, Baranoski JF, Kumandaş S, Minja FJ, Erson-Omay EZ, Mane SM, Lifton RP, Xu T, Keshishian H, Dobyns WB, C. N, Šestan N, Louvi A, Bilgüvar K, Yasuno K, Gleeson JG, Günel M. Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors. Neuron 2014, 84: 1226-1239. PMID: 25521378, PMCID: PMC5024344, DOI: 10.1016/j.neuron.2014.12.014.Peer-Reviewed Original ResearchConceptsComplex cerebral malformationsCerebral cortical malformationsMicrotubule-severing enzyme kataninExome sequencing analysisMitotic spindle formationDrosophila optic lobeCerebral malformationsPatient-derived fibroblastsCell cycle progression delayCortical malformationsMotor neuronsComplex malformationsMicrotubule-associated proteinsCortical developmentReduced cell numberOptic lobeRegulatory subunitBrain developmentCatalytic subunitDeleterious mutationsSpindle formationSupernumerary centrosomesArborization defectsMalformationsHuman phenotypes
2011
Hypomorphic Notch 3 alleles link Notch signaling to ischemic cerebral small-vessel disease
Arboleda-Velasquez JF, Manent J, Lee JH, Tikka S, Ospina C, Vanderburg CR, Frosch MP, Rodríguez-Falcón M, Villen J, Gygi S, Lopera F, Kalimo H, Moskowitz MA, Ayata C, Louvi A, Artavanis-Tsakonas S. Hypomorphic Notch 3 alleles link Notch signaling to ischemic cerebral small-vessel disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: e128-e135. PMID: 21555590, PMCID: PMC3102344, DOI: 10.1073/pnas.1101964108.Peer-Reviewed Original ResearchConceptsSmall vessel diseaseIschemic cerebral small-vessel diseaseCerebral small vessel diseaseGranular osmiophilic materialMouse modelCerebral autosomal dominant arteriopathySmooth muscle cell degenerationBrain vessel pathologyPrevalent human conditionVascular smooth muscle cellsNotch 3 mutationPostmortem human tissueAutosomal dominant arteriopathyTransgenic mouse modelIschemic stroke susceptibilityAge-dependent phenotypeMuscle cell degenerationSmooth muscle cellsNotch-3 receptorCommon monogenic causeIschemic strokeVascular dementiaSubcortical infarctsReceptor activity assaysHuman brain vessels
2010
Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations
Bilgüvar K, Öztürk A, Louvi A, Kwan KY, Choi M, Tatlı B, Yalnızoğlu D, Tüysüz B, Çağlayan A, Gökben S, Kaymakçalan H, Barak T, Bakırcıoğlu M, Yasuno K, Ho W, Sanders S, Zhu Y, Yılmaz S, Dinçer A, Johnson MH, Bronen RA, Koçer N, Per H, Mane S, Pamir MN, Yalçınkaya C, Kumandaş S, Topçu M, Özmen M, Šestan N, Lifton RP, State MW, Günel M. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature 2010, 467: 207-210. PMID: 20729831, PMCID: PMC3129007, DOI: 10.1038/nature09327.Peer-Reviewed Original ResearchConceptsAbnormal cortical developmentWD repeat domain 62 (WDR62) geneSevere brain malformationsWhole-exome sequencingBrain abnormalitiesBrain malformationsCortical developmentMolecular pathogenesisCerebellar hypoplasiaWDR62 mutationsEmbryonic neurogenesisDiagnostic classificationMicrocephaly genesSmall family sizeGenetic heterogeneityWide spectrumRecessive mutationsPachygyriaPathogenesisHypoplasiaNeocortexNeurogenesisAbnormalitiesMalformationsMutations
2008
Developmentally regulated and evolutionarily conserved expression of SLITRK1 in brain circuits implicated in Tourette syndrome
Stillman AA, Krsnik Ž, Sun J, Rašin M, State MW, šestan N, Louvi A. Developmentally regulated and evolutionarily conserved expression of SLITRK1 in brain circuits implicated in Tourette syndrome. The Journal Of Comparative Neurology 2008, 513: 21-37. PMID: 19105198, PMCID: PMC3292218, DOI: 10.1002/cne.21919.Peer-Reviewed Original ResearchConceptsCorticostriatal-thalamocortical circuitsSingle-pass transmembrane proteinTourette syndromeEtiology of TSRare sequence variantsTransmembrane proteinSLITRK1Expression patternsCortical pyramidal neuronsCytoplasmic vesiclesDevelopmental expressionMember 1 geneSequence variantsAxonal repulsionSlit familyDendritic patterningDirect output pathwayCholinergic interneuronsPyramidal neuronsProjection neuronsStriatal expressionMotor ticsSomatodendritic compartmentDevelopmental neuropsychiatric disordersPatch compartmentLinking Notch signaling to ischemic stroke
Arboleda-Velasquez JF, Zhou Z, Shin HK, Louvi A, Kim HH, Savitz SI, Liao JK, Salomone S, Ayata C, Moskowitz MA, Artavanis-Tsakonas S. Linking Notch signaling to ischemic stroke. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 4856-4861. PMID: 18347334, PMCID: PMC2290794, DOI: 10.1073/pnas.0709867105.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsSmooth muscle cellsGenetic rescue experimentsUnderlying cellular pathwaysSpecific gene targetsKnockout mouse modelCellular pathwaysIschemic strokeGene targetsRescue experimentsSMC functionLong-term neurological disabilityMolecular analysisPathophysiology of strokeIschemic phenotypeMuscle cellsNotch-3Neurological disabilityCommon causeMouse modelStriking susceptibilityParaloguesStrokeNotchPhenotype
2005
CCM2 Expression Parallels That of CCM1
Seker A, Pricola KL, Guclu B, Ozturk AK, Louvi A, Gunel M. CCM2 Expression Parallels That of CCM1. Stroke 2005, 37: 518-523. PMID: 16373645, DOI: 10.1161/01.str.0000198835.49387.25.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternBrainCarrier ProteinsCells, CulturedCentral Nervous SystemCerebral CortexChlorocebus aethiopsCOS CellsEndothelium, VascularHumansImmunohistochemistryIn Situ HybridizationKRIT1 ProteinMiceMicrotubule-Associated ProteinsMuscle, SmoothMutationNeuronsPhenotypeProto-Oncogene ProteinsRNA, MessengerSignal TransductionTime FactorsTwo-Hybrid System TechniquesUmbilical VeinsConceptsCerebral cavernous malformationsProtein expressionExtracerebral tissuesFamilial cerebral cavernous malformationsArterial vascular endotheliumPostnatal mouse brainSmooth muscle cellsVascular wall elementsWestern blot analysisExpression patternsPyramidal neuronsVenous circulationCerebral tissueNeurovascular diseasesCavernous malformationsImmunohistochemical analysisVascular endotheliumMouse brainMRNA expressionMuscle cellsFoot processesEpithelial cellsExpression parallelsDisease phenotypeSpatial expression patternsSequence Variants in SLITRK1 Are Associated with Tourette's Syndrome
Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, Morgan TM, Mathews CA, Pauls DL, Rašin M, Gunel M, Davis NR, Ercan-Sencicek AG, Guez DH, Spertus JA, Leckman JF, Dure LS, Kurlan R, Singer HS, Gilbert DL, Farhi A, Louvi A, Lifton RP, Šestan N, State MW. Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome. Science 2005, 310: 317-320. PMID: 16224024, DOI: 10.1126/science.1116502.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdolescentAnimalsAttention Deficit Disorder with HyperactivityBrainChildChild, PreschoolChromosome InversionChromosome MappingChromosomes, Human, Pair 13DNADNA Mutational AnalysisFemaleFrameshift MutationHumansIn Situ Hybridization, FluorescenceMaleMembrane ProteinsMiceMutationNerve Tissue ProteinsPedigreeSequence Analysis, DNATourette SyndromeConceptsSequence variantsTourette syndromeChromosomal inversionsFrameshift mutantsCandidate genesExpression patternsControl chromosomesPrimary neuronal culturesFrameshift mutationSLITRK1Independent occurrenceMotor ticsDevelopmental neuropsychiatric disordersChronic vocalNeuronal culturesIdentical variantsUnrelated probandsBrain regionsNeuropsychiatric disordersSyndrome
2004
Presenilin 1 in migration and morphogenesis in the central nervous system
Louvi A, Sisodia SS, Grove EA. Presenilin 1 in migration and morphogenesis in the central nervous system. Development 2004, 131: 3093-3105. PMID: 15163631, DOI: 10.1242/dev.01191.Peer-Reviewed Original ResearchMeSH KeywordsAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesBrainBrain StemBromodeoxyuridineCell DifferentiationCell DivisionCell MovementCentral Nervous SystemCerebellumColoring AgentsCyclin-Dependent Kinase 5Cyclin-Dependent KinasesCytoskeletonDopamine AgentsEndopeptidasesGene Expression Regulation, DevelopmentalHomozygoteImmunohistochemistryIn Situ HybridizationLightMembrane ProteinsMiceMutationNeuronsPresenilin-1Time FactorsConceptsCentral nervous systemNervous systemPresenilin 1Premature neuronal differentiationCNS morphogenesisCerebral cortexCortical dysplasiaCortical laminationExternal granule layerPontine nucleiPresenilin-1 functionCerebellar granule cell precursorsFacial branchiomotor nucleusTangential migratory pathwayCaudal midbrainGranule cell precursorsNeuronal cellsBrain developmentNeuronal migrationTangential migrationBranchiomotor nucleiCell precursorsNeuronal differentiationGranule layerMidline fusion