Foxg1 Has an Essential Role in Postnatal Development of the Dentate Gyrus
Foxg1 Has an Essential Role in Postnatal Development of the Dentate Gyrus
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Foxg1 在齿状回的产后发育中具有重要作用
DOI：
10.1523/jneurosci.5240-11.2012
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发表时间：
2012-02-29
影响因子：
5.3
通讯作者：
Zhao, Chunjie
中科院分区：
文献类型：
--
作者：
Tian, Chuanxi;Gong, Yifan;Zhao, Chunjie
FOXG1，前身为BF-1，在出生后和成年后的海马齿状回(DG)持续表达。这种转录因子(Tf)被认为参与了以海马体缩小为特征的Rett综合征，表明其在海马区发育中发挥着重要作用。由于FOXG1−/−小鼠的围产期死亡，FOXG1在出生后DG神经发生中的作用仍有待进一步研究。在这里，我们描述了Foxg1fl/fl小鼠系的世代。将FOXG1与Frizzled9-CreERTM系杂交，并与他莫昔芬诱导重组，在出生前和出生后的发育过程中有条件地从DG中去除FOXG1。在这项研究中，我们首先表明FOXG1的破坏导致颗粒下带的丢失和次级放射状胶质支架的严重破坏，导致颗粒细胞的迁移受阻。此外，详细的分析表明，FOXG1可能是维持DG祖细胞库所必需的，而FOXG1的缺失既促进了胶质发生，也促进了神经发生。此外，我们还表明FOXG1可能是有丝分裂后神经元存活和成熟所必需的，并且FOXG1可能参与调节出生后DG发育的Reelin信号。最后，FOXG1的产前缺失表明它很少参与原始颗粒细胞的迁移。综上所述，我们报告FOXG1对于DG的形成是至关重要的，特别是在出生后早期。
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 Foxg1fl/fl mouse line. Foxg1 was conditionally ablated from the DG during prenatal and postnatal development by crossing this line with a Frizzled9-CreERTM 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.