Foxg1 upregulation enhances neocortical activity

Wendalina Tigani, Moira Pinzan Rossi, Osvaldo Artimagnella, Manuela Santo, Rossana Rauti, Teresa Sorbo, Francesco Paolo Ulloa Severino, Giovanni Provenzano, Manuela Allegra, Matteo Caleo, Laura Ballerini, Yuri Bozzi, Antonello Mallamaci*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Foxg1 is an ancient transcription factor gene orchestrating a number of neurodevelopmental processes taking place in the rostral brain. In this study, we investigated its impact on neocortical activity.We found that mice overexpressing Foxg1 in neocortical pyramidal cells displayed an electroencephalography (EEG) with increased spike frequency and were more prone to kainic acid (KA)-induced seizures. Consistently, primary cultures of neocortical neurons gain-of-function for Foxg1 were hyperactive and hypersynchronized. That ref lected an unbalanced expression of key genes encoding for ion channels, gamma aminobutyric acid and glutamate receptors, and was likely exacerbated by a pronounced interneuron depletion.We also detected a transient Foxg1 upregulation ignited in turn by neuronal activity and mediated by immediate early genes. Based on this, we propose that even small changes of Foxg1 levels may result in a profound impact on pyramidal cell activity, an issue relevant to neuronal physiology and neurological aberrancies associated to FOXG1 copy number variations.

Original languageEnglish
Pages (from-to)5147-5165
Number of pages19
JournalCerebral Cortex
Issue number9
StatePublished - 1 Sep 2020


  • Foxg1
  • Immediate early genes
  • Neuron hyperactivity
  • West syndrome


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