The Regulation Of Foxg1 In The Postnatal Development Of Cortical Interneurons

The high level of cognitive function of the cerebral cortex is dependent on the coordination of two important classes of neurons:excitatory projection neurons and inhibitory interneurons.Of these,although the interneurons only consists of 20%-30%of all cortical neurons,it plays important roles in the neural circuit.By receiving the excitatory signals of the projected neurons,interneurons regulate the excitatory/inhibitory balance of the neural circuit.Abnormal development of the interneurons often cause avariety of neurodevelopmental diseases,including epilepsy,Rett syndrome,West syndrome and many emotional disorders.Although interneurons play key roles in regulating cortical function,the mechanism of development of cortical interneurons is still unclear.Foxgl is a transcription factor with important functions for telencephalic development.Patients with Foxgl syndrome suffer from microcephaly,retardation,mentalretardation,and most of the patients accompanied by the occurrence of epilepsy.All these phenomenon suggest that Foxgl may participate in the regulation of the development of interneurons.Previously we have shown Foxgl is required for the embryonic cortical interneuron development.Deficiency of Foxgl leads to abnormal tangential migration of the cortical interneurons.However,perinatal death of the Dlx5/6-cre;Foxg1fl/fl mutant making it unachievable to reveal the function of Foxgl in postnatal development of interneurons.In this study we investigated the role of Foxgl in the development of cortical interneurons during postnatal period.Conditional deletion of Foxgl was achieved by crossing Foxg1fl/fl mice with Gad2-CreER combined with tamoxifen induction at P1.Time-specific knock out of the Foxgl resulted in abnormal distributions of SST-,NPY-and CR-positive interneurons and changed in number of CR-,PV-and VIP-positive intemeurons.Compared with the control group,we found the total length of dendrites of the interneurons was increased in mutants,and the branches were more complicated.To further explore the molecular mechanisms,we found that Cxcr4 one of the migration-related receptors and transcription factor Dlxl,were down-regulated.In conclusion,our results show that Foxgl plays an important role in the development of interneurons during the postnatal period and Foxgl acts as the up stream regulator of Cxcr4 and Dlxl to control the radial migration and differentiation of cortical interneurons.These findings are helpful for us to further understand the development of interneurons.