title: Disruptions in asymmetric centrosome inheritance and WDR62-Aurora kinase B interactions in primary microcephaly.
abstract: Recessive mutations in WD repeat domain 62 (WDR62) cause microcephaly and a wide spectrum of severe brain malformations. Disruption of the mouse ortholog results in microcephaly underlain by reduced proliferation of neocortical progenitors during late neurogenesis, abnormalities in asymmetric centrosome inheritance leading to neuronal migration delays, and altered neuronal differentiation. Spindle pole localization of WDR62 and mitotic progression are defective in patient-derived fibroblasts, which, similar to mouse neocortical progenitors, transiently arrest at prometaphase. Expression of WDR62 is closely correlated with components of the chromosome passenger complex (CPC), a key regulator of mitosis. Wild type WDR62, but not disease-associated mutant forms, interacts with the CPC core enzyme Aurora kinase B and staining of CPC components at centromeres is altered in patient-derived fibroblasts. Our findings demonstrate critical and diverse functions of WDR62 in neocortical development and provide insight into the mechanisms by which its disruption leads to a plethora of structural abnormalities.
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Sgourdou
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Ketu
authors.initials: K
authors.lastname: Mishra-Gorur
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Ichiko
authors.initials: I
authors.lastname: Saotome
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Octavian
authors.initials: O
authors.lastname: Henagariu
authors.affiliation: Department of Pediatric Genetics, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tuysuz
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Campos
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishigame
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Krinio
authors.initials: K
authors.lastname: Giannikou
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Quon
authors.affiliation: Departments of Neuroscience, Genetics and Psychiatry, Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Nenad
authors.initials: N
authors.lastname: Sestan
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.|Department of Medical Genetics, School of Medicine, Istanbul Bilim University, Istanbul, Turkey.
authors.forename: Ahmet O
authors.initials: AO
authors.lastname: Caglayan
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.|Department of Genetics, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Murat
authors.initials: M
authors.lastname: Gunel
authors.affiliation: Departments of Neurosurgery and Neuroscience, Program on Neurogenetics, Yale School of Medicine, New Haven, CT, 06520, USA.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Louvi
mesh_terms: D000818:Animals; D064107:Aurora Kinase B / Q000235:genetics*; D001921:Brain / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism*; D003241:Consanguinity; D004195:Disease Models, Animal; D004843:Epistasis, Genetic; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008831:Microcephaly / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D058953:Neural Stem Cells / Q000378:metabolism; D010375:Pedigree; D000073336:Whole Genome Sequencing
chemical_list: D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; C552527:WDR62 protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B