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

Written By Peter Slavish

First Author: Jessica Mariani (More authors)
Journal: Cell
Year: 2015

iPSC neurons generated from families with a proband dx with idiopathic ASD and increased head circumference; FOXG1 expression consistently shown to be upregulated in these individuals.

shRNA designed to target and downregulate FOXG1 expression; when ASD-derived iPSC cells treated, FOXG1 expression levels lowered to a level similar to their unaffected controls, with downregulation of GABAergic markers, with restoration to the normal level of GABAergic neuronal differentiation. Evidence also suggest upregulation of FOXG1 in ASD neural cells is an early driving force for proliferation of npcs of GABAergic lineage.

In ASD, larger head size has been associated with more severe symptoms and lower IQ; in 9 individuals with ASD and a larger head size; increased FOXG1 expression correlated with greater head size.

Significance
Implicates FOXG1 dysregulation in the pathogenesis of autism spectrum disorders, and possible in head size.

Peter Slavish
Previous

RNA activation of haploinsufficient Foxg1 gene in murine neocortex
Next

Imbalance of excitatory/inhibitory synaptic protein expression in iPSC-derived neurons from FOXG1 patients and in foxg1 mice