The HSA21 gene EURL/C21ORF91 controls neurogenesis within the cerebral cortex and is implicated in the pathogenesis of Down Syndrome
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
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 2013Maxwell, 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: ...
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 ...