Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    The HSA21 gene EURL/C21ORF91 controls neurogenesis within the cerebral cortex and is implicated in the pathogenesis of Down Syndrome

    Access Status
    Open access via publisher
    Authors
    Li, S.
    Qu, Z.
    Haas, M.
    Ngo, L.
    Heo, Y.
    Kang, H.
    Britto, J.
    Cullen, H.
    Vanyai, H.
    Tan, S.
    Chan-Ling, T.
    Gunnersen, J.
    Heng, Julian
    Date
    2016
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Li, S. and Qu, Z. and Haas, M. and Ngo, L. and Heo, Y. and Kang, H. and Britto, J. et al. 2016. The HSA21 gene EURL/C21ORF91 controls neurogenesis within the cerebral cortex and is implicated in the pathogenesis of Down Syndrome. Scientific Reports. 6: 29514.
    Source Title
    Scientific Reports
    DOI
    10.1038/srep29514
    ISSN
    2045-2322
    School
    Health Sciences Research and Graduate Studies
    URI
    http://hdl.handle.net/20.500.11937/71499
    Collection
    • Curtin Research Publications
    Abstract

    Copy number variations to chromosome 21 (HSA21) cause intellectual disability and Down Syndrome, but our understanding of the HSA21 genetic factors which contribute to fetal brain development remains incomplete. Here, we focussed on the neurodevelopmental functions for EURL (also known as C21ORF91, Refseq Gene ID:54149), a protein-coding gene at the centromeric boundary of the Down Syndrome Critical Region (DSCR) of HSA21. We report that EURL is expressed during human and mouse cerebral cortex development, and we report that alterations to EURL mRNA levels within the human brain underlie Down Syndrome. Our gene perturbation studies in mice demonstrate that disruptions to Eurl impair progenitor proliferation and neuronal differentiation. Also, we find that disruptions to Eurl impair the long-term positioning and dendritic spine densities of cortical projection neurons. We provide evidence that EURL interacts with the coiled-coil domain-containing protein CCDC85B so as to modulate ß-catenin levels in cells. Further, we utilised a fluorescent reporter (8xTOPFLASHd2EGFP) to demonstrate that disruptions to Eurl alter ß-catenin signalling in vitro as well as in vivo. Together, these studies highlight EURL as an important new player in neuronal development that is likely to impact on the neuropathogenesis of HSA21-related disorders including Down Syndrome.

    Related items

    Showing items related by title, author, creator and subject.

    • Validating the Rett Syndrome Gross Motor Scale
      Downs, Jennepher; Stahlhut, M.; Wong, K.; Syhler, B.; Bisgaard, A.; Jacoby, P.; Leonard, H. (2016)
      © 2016 Downs et al. Rett syndrome is a pervasive neurodevelopmental disorder associated with a pathogenic mutation on the MECP2 gene. Impaired movement is a fundamental component and the Rett Syndrome Gross Motor Scale ...
    • Impact of prenatal screening and diagnostic testing on trends in Down syndrome births and terminations in Western Australia 1980 to 2013
      Maxwell, S.; Bower, C.; O'Leary, Peter (2015)
      © 2015 John Wiley & Sons, Ltd. Objective: To assess how prenatal screening and diagnostic testing have impacted the diagnosis, termination and birth prevalence of Down syndrome in Western Australia (1980-2013). Method: ...
    • Parent-reported health-related quality of life of children with Down syndrome: a descriptive study
      Shields, N.; Leonard, H.; Munteanu, S.; Bourke, J.; Lim, P.; Taylor, N.; Downs, Jennepher (2018)
      © 2018 Mac Keith Press Aim: To describe health-related quality of life of Australian children and adolescents with Down syndrome and compare it with norm-referenced data. Method: A cross-sectional survey was conducted ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.