2023
Microcephaly-associated protein WDR62 shuttles from the Golgi apparatus to the spindle poles in human neural progenitors
Dell'Amico C, Salavarria M, Takeo Y, Saotome I, Dell'Anno M, Galimberti M, Pellegrino E, Cattaneo E, Louvi A, Onorati M. Microcephaly-associated protein WDR62 shuttles from the Golgi apparatus to the spindle poles in human neural progenitors. ELife 2023, 12: e81716. PMID: 37272619, PMCID: PMC10241521, DOI: 10.7554/elife.81716.Peer-Reviewed Original ResearchConceptsHuman fetal brain tissueStructural brain abnormalitiesC-terminal truncating mutationsFetal brain tissueEtiology of microcephalySevere neurodevelopmental abnormalitiesStem cellsNeuroepithelial stem cellsHuman neural progenitorsHuman brain developmentBrain abnormalitiesCommon causeNeurodevelopmental abnormalitiesAutosomal recessive primary microcephalyBrain tissueBrain developmentCerebral organoidsMicrocephalyUnaffected parentsTruncating mutationsNeural progenitorsHuman neurodevelopmentAbnormalitiesPleiotropic functionsCritical hub
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
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