Foxg1 Regulates the Postnatal Development of Cortical Interneurons.
Foxg1 Regulates the Postnatal Development of Cortical Interneurons.
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Foxg1 调节皮质中间神经元的产后发育。
DOI：
10.1093/cercor/bhy051
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Zhao Chunjie
中科院分区：
文献类型：
--
作者：
Shen Wei;Ba Ru;Su Yan;Ni Yang;Chen Dongsheng;Xie Wei;Pleasure Samuel J;Zhao Chunjie
皮层中间神经元的缺失与神经系统疾病密切相关。大多数Foxg 1综合征患者会出现癫痫发作，这表明Foxg 1可能在皮质中间神经元发育中发挥作用。在此，通过Foxg 1 fl/fl与Gad 2-CreER系杂交，条件性缺失Foxg 1，我们发现出生后生长抑素、钙视网膜蛋白和神经肽Y阳性中间神经元在皮质的分布受损。进一步的研究显示Foxg 1缺陷的中间神经元的树突复杂性增强，迁移能力降低，伴随着Dlx 1和CXCR 4的显著下调。过表达Dlx 1或敲低其下游的Pak 3可挽救分化缺陷，说明Foxg 1在Dlx 1-Pak 3信号通路上游发挥调控皮质中间神经元生后发育的作用。由于神经回路的不平衡，Foxg 1突变体表现出癫痫发作的易感性增加。这些发现将提高我们对中间神经元出生后发育的理解，并有助于阐明携带Foxg 1突变的患者癫痫发作的潜在机制。
Abnormalities in cortical interneurons are closely associated with neurological diseases. Most patients with Foxg1 syndrome experience seizures, suggesting a possible role of Foxg1 in the cortical interneuron development. Here, by conditional deletion ofFoxg1, which was achieved by crossingFoxg1fl/flwith theGad2-CreERline, we found the postnatal distributions of somatostatin-, calretinin-, and neuropeptide Y-positive interneurons in the cortex were impaired. Further investigations revealed an enhanced dendritic complexity and decreased migration capacity ofFoxg1-deficient interneurons, accompanied by remarkable downregulation of Dlx1 and CXCR4. Overexpression of Dlx1 or knock down its downstream Pak3 rescued the differentiation detects, demonstrated that Foxg1 functioned upstream of Dlx1-Pak3 signal pathway to regulate the postnatal development of cortical interneurons. Due to the imbalanced neural circuit,Foxg1mutants showed increased seizure susceptibility. These findings will improve our understanding of the postnatal development of interneurons and help to elucidate the mechanisms underlying seizure in patients carryingFoxg1mutations.