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Human genetic studies have established a link between a class of centrosome proteins and microcephaly. Current studies of microcephaly focus on defective centrosome/spindle orientation. Mutations in WDR62 are associated with microcephaly and other cortical abnormalities in humans. Here we create a mouse model of Wdr62 deficiency and find that the mice exhibit reduced brain size due to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and cell death. Mechanistically, Wdr62 associates and genetically interacts with Aurora A to regulate spindle formation, mitotic progression and brain size. Our results suggest that Wdr62 interacts with Aurora A to control mitotic progression, and loss of these interactions leads to mitotic delay and cell death of NPCs, which could be a potential cause of human microcephaly.
Pubmed ID: 24875059
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Software tool for identification and annotation of genetically mobile domains and analysis of domain architectures.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsMus musculus with name 129S1/SvImJ from IMSR.
View all literature mentionsNational public repository system for mutant mice. Archives and distributes scientifically valuable spontaneous and induced mutant mouse strains and ES cell lines for use by biomedical research community. Includes breeding/distribution facilities and information coordinating center. Mice strains are cryopreserved, unless live colony must be established. Live mice are supplied from production colony, from colony recovered from cryopreservation, or via micro-injection of cell line into host blastocysts. MMRRC member facilities also develop technologies to improve handling of mutant mice, including advances in assisted reproductive techniques, cryobiology, genetic analysis, phenotyping and infectious disease diagnostics.
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