Impaired Interneuron Development after Foxg1 Disruption.

Interneurons play pivotal roles in the modulation of cortical function; however, the mechanisms that control interneuron development remain unclear. This study aimed to explore a new role for Foxg1 in interneuron development. By crossing Foxg1fl/fl mice with a Dlx5/6-Cre line, we determined that conditional disruption of Foxg1 in the subpallium results in defects in interneuron development. In developing interneurons, the expression levels of several receptors, including roundabout-1, Eph receptor A4, and C-X-C motif receptor 4/7, were strongly downregulated, which led to migration defects after Foxg1 ablation. The transcription factors Dlx1/2 and Mash1, which have been reported to be involved in interneuron development, were significantly upregulated at the mRNA levels. Foxg1 mutant cells developed shorter neurites and fewer branches and displayed severe migration defects in vitro. Notably, Prox1, which is a transcription factor that functions as a key regulator in the development of excitatory neurons, was also dramatically upregulated at both the mRNA and protein levels, suggesting that Prox1 is also important for interneuron development. Our work demonstrates that Foxg1 may act as a critical upstream regulator of Dlx1/2, Mash1, and Prox1 to control interneuron development. These findings will further our understanding of the molecular mechanisms of interneuron development.