FoxG1 function in hippocampus

The forkhead box transcription factor FoxG1 is known to influence forebrain development by determining regional brain specification as well as by regulating expansion of neuronal progenitors and timing of their differentiation. In the adult brain, FoxG1 is expressed in cortex and hippocampus. In the latter it is involved in postnatal neurogenesis in the dentate gyrus by influencing maintenance of the progenitor pool as well as survival and maturation of postmitotic neurons. In humans, haploinsufficiency of FoxG1 causes the congenital version of the Rett syndrome, a progressive neurologic developmental disorder. We use FoxG1 mutant mice to screen for global changes in mRNA expression after partial loss of FoxG1 protein in hippocampi of six week-old mice. Data analysis points to a specific function for FoxG1 in adult hippocampus besides its known involvement in dentate gyrus neurogenesis. We analyse transcriptional changes in the different CA-fields and show that especially the CA-1 field is influenced by lack of FOXG1 protein. Furthermore, data analysis shows altered expression of genes that have also been implicated in the classical form of the Rett syndrome and other autism spectrum disorders.

叉头框转录因子FoxG1（forkhead box transcription factor FoxG1）已被证实可通过调控脑区域特化、神经元祖细胞的扩增及其分化时序，影响前脑发育。在成年大脑中，FoxG1于大脑皮层与海马体中表达。在海马体中，其通过影响祖细胞库的维持，以及有丝分裂后神经元的存活与成熟，参与齿状回的产后神经发生过程。在人类中，FoxG1单倍剂量不足会引发先天性瑞特综合征（Rett syndrome）——一种进行性神经发育障碍。本研究利用FoxG1突变小鼠，对6周龄小鼠海马体中FoxG1蛋白部分缺失后的mRNA表达全局变化进行筛选。数据分析表明，除已知的参与齿状回神经发生外，FoxG1在成年海马体中还存在特定功能。我们分析了海马不同CA区的转录变化，结果显示，尤其是CA1区会因FOXG1蛋白缺失而受到显著影响。此外，数据分析还显示，部分与经典型瑞特综合征及其他自闭症谱系障碍相关的基因表达发生了改变。