Journal article
A Primate-Specific Isoform of PLEKHG6 Regulates Neurogenesis and Neuronal Migration
AC O'Neill, C Kyrousi, J Klaus, RJ Leventer, EP Kirk, A Fry, DT Pilz, T Morgan, ZA Jenkins, M Drukker, SF Berkovic, IE Scheffer, R Guerrini, DM Markie, M Götz, S Cappello, SP Robertson
Cell Reports | CELL PRESS | Published : 2018
Open access
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..
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Awarded by University of Otago
Funding Acknowledgements
We thank the families for their participation in this study. The Exome Aggregation Consortium is acknowledged for access to data, as are Marta Florio and Wieland Huttner for the investigation of PLEKHG6 isoform expression in fetal tissue. The authors also thank Kalina Draganova for insightful feedback on the manuscript. R.G. is supported by funding from the European Union through the Seventh Framework Programme (FP7) under the project DESIRE (N602531). M.G. is supported by funding from the European Research Council (ERC) grant ChroNeuroRepair. S.P.R. is supported by funding from the Health Research Council of New Zealand and Cure Kids NZ. S.C. is supported by funding from the German Research Foundation grant CA 1205/2-1. A.C.O. was supported by a grant from the Deutshcer Akademischer Austauschdienst of the German Research Council, a University of Otago Postgraduate Scholarship Award, and a Philip Wrightson Postdoctoral Fellowship from the Neurological Foundation of New Zealand.