Differential vulnerability of adult neurogenic niches to dosage of the Neurodevelopmental-disorder linked gene FoxG1

We report that the two adult neurogenic niches of the mammalian brain – the dentate gyrus of the hippocampal formation and the subependymal zone of the lateral ventricles - displayed differential vulnerability to increased FoxG1 dosage: high FoxG1 levels severely compromised survival and glutamatergic dentate granule neuron fate acquisition in the hippocampal neurogenic niche, but left neurogenesis of GABAergic neurons in the subependymal zone / olfactory bulb system unaffected. Comparative transcriptomic analyses revealed a significantly higher expression of the apoptosis-linked nuclear receptor Nr4a1 in FoxG1-overexpressing hippocampal neural precursors. Our results reveal differential vulnerability of neuronal subtypes to increased FoxG1 dosage and suggest that activity of a FoxG1/Nr4a1 axis contributes to such subtype-specific response. Overall design: Bulk RNA-sequencing from adult neural stem/progenitor cells (NSPCs) derived from either the dentate gyrus or the subepenymal zone of female adult C57BL/6. Both groups were transduced with either a CAG-GFP control retrovirus or a FoxG1-overexpressing (CAG-FoxG1-IRES-GFP) retrovirus.