ASPM is a major determinant of cerebral cortical size

Jacquelyn Bond, Emma Roberts, Ganesh H. Mochida, Daniel J. Hampshire, Sheila Scott, Jonathan M. Askham, Kelly Springell, Meera Mahadevan, Yanick J. Crow, Alexander F. Markham, Christopher A. Walsh, C. Geoffrey Woods

    Research output: Contribution to journalArticlepeer-review

    Abstract

    One of the most notable trends in mammalian evolution is the massive increase in size of the cerebral cortex, especially in primates. Humans with autosomal recessive primary microcephaly (MCPH) show a small but otherwise grossly normal cerebral cortex associated with mild to moderate mental retardation1-4. Genes linked to this condition offer potential insights into the development and evolution of the cerebral cortex. Here we show that the most common cause of MCPH is homozygous mutation of ASPM, the human ortholog of the Drosophila melanogaster abnormal spindle gene (asp)s, which is essential for normal mitotic spindle function in embryonic neuroblasts6. The mouse gene Aspm is expressed specifically in the primary sites of prenatal cerebral cortical neurogenesis. Notably, the predicted ASPM proteins encode systematically larger numbers of repeated 'IQ' domains between flies, mice and humans, with the predominant difference between Aspm and ASPM being a single large insertion coding for IQ domains. Our results and evolutionary considerations suggest that brain size is controlled in part through modulation of mitotic spindle activity in neuronal progenitor cells.
    Original languageEnglish
    Pages (from-to)316-320
    Number of pages4
    JournalNature Genetics
    Volume32
    Issue number2
    DOIs
    Publication statusPublished - 1 Oct 2002

    Keywords

    • Anthropometry
    • Blotting, Northern
    • anatomy & histology: Cerebral Cortex
    • Codon, Nonsense
    • Drosophila Proteins
    • Female
    • Humans
    • Male
    • genetics: Microcephaly
    • genetics: Microtubule-Associated Proteins
    • genetics: Nerve Tissue Proteins
    • Pedigree
    • Sequence Analysis, DNA

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