Foxg1 Has an Essential Role in Postnatal Development of the Dentate Gyrus

Foxg1, formerly BF-1, is expressed continuously in the postnatal and adult hippocampal dentate gyrus (DG). This transcription factor (TF) is thought to be involved in Rett syndrome, which is characterized by reduced hippocampus size, indicating its important role in hippocampal development. Due to the perinatal death of Foxg1(-/-) mice, the function of Foxg1 in postnatal DG neurogenesis remains to be explored. Here, we describe the generation of a Foxg1(fl/fl) mouse line. Foxg1 was conditionally ablated from the DG during prenatal and postnatal development by crossing this line with a Frizzled9-CreER (TM) line and inducing recombination with tamoxifen. In this study, we first show that disruption of Foxg1 results in the loss of the subgranular zone and a severely disrupted secondary radial glial scaffold, leading to the impaired migration of granule cells. Moreover, detailed analysis reveals that Foxg1 may be necessary for the maintenance of the DG progenitor pool and that the lack of Foxg1 promotes both gliogenesis and neurogenesis. We additionally show that Foxg1 may be required for the survival and maturation of postmitotic neurons and that Foxg1 may be involved in Reelin signaling in regulating postnatal DG development. Last, prenatal deletion of Foxg1 suggests that it is rarely involved in the migration of primordial granule cells. In summary, we report that Foxg1 is critical for DG formation, especially during early postnatal stage.