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https://ahro.austin.org.au/austinjspui/handle/1/19975| Title: | A Primate-Specific Isoform of PLEKHG6 Regulates Neurogenesis and Neuronal Migration. | Austin Authors: | O'Neill, Adam C;Kyrousi, Christina;Klaus, Johannes;Leventer, Richard J;Kirk, Edwin P;Fry, Andrew;Pilz, Daniela T;Morgan, Tim;Jenkins, Zandra A;Drukker, Micha;Berkovic, Samuel F ;Scheffer, Ingrid E ;Guerrini, Renzo;Markie, David M;Götz, Magdalena;Cappello, Silvia;Robertson, Stephen P | Affiliation: | Institute of Medical Genetics, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia Institute of Stem Cell Research, Helmholtz Center, Munich, Germany Max Planck Institute of Psychiatry, Munich, Germany Institute of Stem Cell Research, Helmholtz Center, Munich, Germany Physiological Genomics, Biomedical Center Ludwig-Maximilians-Universitaet, Munich, Germany Excellence Cluster of Systems Neurology (SYNERGY), 82152 Planegg/Martinsried, Germany West of Scotland Genetics Service, Laboratory Medicine Building, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia Department of Neurology, Murdoch Children's Research Institute, Parkville, Victoria, Australia Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia Sydney Children's Hospital, University of New South Wales, Randwick, NSW, Australia New South Wales Health Pathology, Randwick, NSW, Australia Department of Women's and Children's Health, University of Otago, Dunedin, New Zealand Pediatric Neurology Unit and Laboratories, Children's Hospital A. Meyer-University of Florence, Florence, Italy Department of Pathology, University of Otago, Dunedin, New Zealand Max Planck Institute of Psychiatry, Munich, Germany |
Issue Date: | 4-Dec-2018 | Publication information: | Cell reports 2018; 25(10): 2729-2741.e6 | Abstract: | The mammalian neocortex has undergone remarkable changes through evolution. A consequence of such rapid evolutionary events could be a trade-off that has rendered the brain susceptible to certain neurodevelopmental and neuropsychiatric conditions. We analyzed the exomes of 65 patients with the structural brain malformation periventricular nodular heterotopia (PH). De novo coding variants were observed in excess in genes defining a transcriptomic signature of basal radial glia, a cell type linked to brain evolution. In addition, we located two variants in human isoforms of two genes that have no ortholog in mice. Modulating the levels of one of these isoforms for the gene PLEKHG6 demonstrated its role in regulating neuroprogenitor differentiation and neuronal migration via RhoA, with phenotypic recapitulation of PH in human cerebral organoids. This suggests that this PLEKHG6 isoform is an example of a primate-specific genomic element supporting brain development. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/19975 | DOI: | 10.1016/j.celrep.2018.11.029 | ORCID: | 0000-0002-2311-2174 0000-0003-4580-841X |
Journal: | Cell reports | PubMed URL: | 30517861 | Type: | Journal Article | Subjects: | MyoGEF PLEKHG6 RhoA cortical development evolution periventricular heterotopia |
| Appears in Collections: | Journal articles |
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