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

First Author: Tommaso Patriarchi (More authors)
Journal: European Journal of Human Genetics
Year: 2016

iPSC neurons generated from fibroblasts of two individuals with FOXG1 syndrome, one carrying a truncating variant, and the other with a deletion including the entire FOXG1 gene.

Similar to what is found in iPSC neurons from individuals with CDKL5 or MECP2-related disorders, expression of the gene, GRID1, was significantly increased in FOXG1-derived neurons. To compare the relative amounts of excitatory vs. inhibitory synapses, the expression of related gene markers were analyzed; those associated with inhibitory synapses were increased, whereas those with excitatory synapses were decreased. The authors propose that this imbalance may be contributing to the neurodevelopmental features observed in FOXG1 syndrome.

Significance
First published use of iPSC neurons derived from individuals with FOXG1 syndrome; a phenotype is identified, which can be used as a marker in future experiments to measure the success of potential therapies.