Foxg1 Regulates The Development Of Cortical Interneurons

Interneurons play pivotal roles in the modulation of cortical function;however the mechanisms that control interneuron development remain unclea:r.This study aimed to explore a new role for Foxgl in interneuron development.By crossing Foxglfl/fl mice with a Dlx5/6-Cre line,we determined that conditional disruption of Foxgl 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 down-regulated,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 up-regulated at the mRNA levels.Foxgl mutant cells developed shorter neurites and fewer branches and displayed severe migration defects in vitro.Notably,Proxl,which is a transcription factor that functions as a key regulator in the development of excitatory neurons,was also dramatically up-regulated at both the mRNA and protein levels,suggesting that Prox1 is also important for interneuron development.Our work demonstrates that Foxgl may act as a critical up-stream regulator of Dlx1/2,Mash1 and Proxl to control interneuron development.These findings will further our understanding of the molecular mechanisms of interneuron development.