The Function Of FOXG1 In The Development Of Spiny Projection Neurons

The striatum which is differentiated from the lateral ganglion eminence is located in the ventral telencephalon,and is the main input-output part of the basal ganglia.The striatum is the main information processing center of the basal ganglia.After receiving input information from different telencephalon parts and integrating information,the striatum transmits instructions to other parts of basal ganglia through direct and indirect output pathways,so as to regulate motor behavior.Striatal neurons include ～95% spiny projection neurons and ～5% striatal intermediate neurons.Spiny projection neurons are involved in the regulation of striatal output pathway and include two subtypes,direct pathway spiny projection neurons and indirect pathway spiny projection neurons.Direct pathway spiny projection neurons promote motor function,indirect pathway spiny projection neurons inhibit motor function.Abnormal development of these two subtypes of spiny projection neurons leads to an imbalance between the two striatal output pathways,which leads to striatal related dyskinesia.The research of spiny projection neurons’ development will provide important clues for the pathogenesis and treatment strategies of related diseases.FOXG1 syndrome is caused by the mutations of FOXG1 gene.Patients exhibit cognitive dysfunction and psychiatric disorders,and suffer from mixed dyskinesia such as dystonia,chorea and athetosis,suggesting that FOXG1 may be related to the development of spiny projection neurons.In this study,Foxg1 is specifically deleted in the striatal progenitors and postmitotic neurons to explore the role of FOXG1 in the subtype specification of spiny projection neurons.We find that the total number of spiny projection neurons and the two subtypes of spiny projection neurons are significantly reduced at E18.5 days after Foxg1 deletion in the striatal progenitors.Further studies show that the specification of neurons subtype is blocked,and normal fate of direct and indirect pathway spiny projection neurons could not be obtained.In the postmitotic direct pathway spiny projection neurons which are specifically deleted Foxg1,we find that direct pathway spiny projection neurons abnormally express specific molecular markers which normally express in indirect pathway spiny projection neurons.These results demonstrate that FOXG1 inhibits the specification of indirect pathway spiny projection neurons and promotes the specification of direct pathway spiny projection neurons.Our study suggests that the deletion of Foxg1 leads to abnormal subtype specification of spiny projection neurons,which may be one of the causes of dyskinesia in FOXG1 syndrome.This study is useful to elucidate the developmental regulatory mechanisms underlying the development of spiny projection neurons and lays a foundation for further understanding the pathogenesis of FOXG1 syndrome.