Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/19975
Title: A Primate-Specific Isoform of PLEKHG6 Regulates Neurogenesis and Neuronal Migration.
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
Department of Women's and Children's Health, University of Otago, Dunedin, New Zealand; 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, VIC, Australia
Department of Paediatrics, University of Melbourne, Parkville, VIC, 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
Department of Women's and Children's Health, University of Otago, Dunedin, New Zealand
Issue Date: 4-Dec-2018
Citation: 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: http://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
PubMed URL: 30517861
Type: Journal Article
Subjects: MyoGEF
PLEKHG6
RhoA
cortical development
evolution
periventricular heterotopia
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.