Foxg1 Regulates the Postnatal Development of Cortical Interneurons

Cereb Cortex. 2019 Apr 1;29(4):1547-1560. doi: 10.1093/cercor/bhy051.


Abnormalities in cortical interneurons are closely associated with neurological diseases. Most patients with Foxg1 syndrome experience seizures, suggesting a possible role of Foxg1 in the cortical interneuron development. Here, by conditional deletion of Foxg1, which was achieved by crossing Foxg1fl/fl with the Gad2-CreER line, we found the postnatal distributions of somatostatin-, calretinin-, and neuropeptide Y-positive interneurons in the cortex were impaired. Further investigations revealed an enhanced dendritic complexity and decreased migration capacity of Foxg1-deficient interneurons, accompanied by remarkable downregulation of Dlx1 and CXCR4. Overexpression of Dlx1 or knock down its downstream Pak3 rescued the differentiation detects, demonstrated that Foxg1 functioned upstream of Dlx1-Pak3 signal pathway to regulate the postnatal development of cortical interneurons. Due to the imbalanced neural circuit, Foxg1 mutants showed increased seizure susceptibility. These findings will improve our understanding of the postnatal development of interneurons and help to elucidate the mechanisms underlying seizure in patients carrying Foxg1 mutations.

Keywords: CXCR4; Dlx1; Foxg1; interneuron; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement
  • Cerebral Cortex / growth & development*
  • Cerebral Cortex / metabolism
  • Epilepsy / etiology
  • Epilepsy / physiopathology
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Forkhead Transcription Factors / physiology*
  • Homeodomain Proteins / metabolism
  • Interneurons / physiology*
  • Male
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Receptors, CXCR4 / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism
  • p21-Activated Kinases / metabolism


  • CXCR4 protein, mouse
  • Distal-less homeobox proteins
  • Forkhead Transcription Factors
  • Foxg1 protein, mouse
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Receptors, CXCR4
  • Transcription Factors
  • Pak3 protein, mouse
  • p21-Activated Kinases