O que diferencia os primatas de outros mamíferos? Somente um gene?

segunda-feira, dezembro 10, 2018

A Primate-Specific Isoform of PLEKHG6 Regulates Neurogenesis and Neuronal Migration

Adam C. O’Neill Christina Kyrousi Johannes Klaus Richard J. Leventer Edwin P. Kirk Andrew Fry Daniela T. Pilz Tim Morgan Zandra A. Jenkins Micha Drukker  Samuel F. Berkovic Ingrid E. Scheffer Renzo Guerrini David M. Markie Magdalena Götz Silvia Cappello 16, 17 Stephen P. Robertson 16

Open AccessPublished: December 4, 2018  

Graphical Abstract:

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• Excess variants within basal radial glia transcriptomic signatures in cases of PH

• PLEKHG6 primate-specific isoform mutated in a case of PH functions via RhoA

• PLEKHG6 isoforms regulate features of neurogenesis

• Modulation of the PLEKHG6 primate isoform reproduces features of PH in organoids


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.