RNA activation of haploinsufficient Foxg1 gene in murine neocortex

First Author: Cristina Fimiani (More authors)
Journal: Scientific Reports
Year: 2016

Foxg1-RNAa delivered to murine E12.5 neocortical precursors by lentivirus; expression increase ranged from 1.28-2.88 fold increase. Increasing Foxg1expression in proliferating murine neocortical precursors decreased the number of neurons generated.

By delivering the RNAa molecule to specific neuronal populations, the authors provided evidence to suggest that ectopic (or off-target) up-regulation of Foxg1expression would not be significant.

Delivery of a similar miR molecule using an AAV9 system into newly born mouse pups showed modest upregulation of Foxg1 expression in the brain.

Significance
Demonstrates efficacy of using RNA activation to boost endogenous expression of Foxg1; this is a potential therapeutic strategy to alleviate clinical symptoms of FOXG1 syndrome

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FOXG1 syndrome: genotype-phenotype association in 83 patients with FOXG1 variants

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FOXG1-dependent dysregulation of GABA/Glutamatergic neuron differentiation in autism spectrum disorders