Fibroblast growth factor 9 (FGF9) is a member of the fibroblast growth factor family and is widely expressed in the central nervous system (CNS). However, it is not clear how the working mechanism of FGF9 is involved in cerebellar development. To address this question, we deleted the Fgf9 gene specifically in GABAergic neurons or glutamatergic neurons, and demonstrated that Fgf9 ablation in GABAergic neurons rather than the glutamatergic neurons caused severe ataxia. We showed that FGF9 played a key role in the survival and development of Purkinje cells. GABAergic neuron-specific knockout of FGF9 (Fgf9VGAT) significantly affected the survival and development of Purkinje cells, disrupting Bergmann fiber scaffold formation and granule neuron migration in mice. RNA sequencing revealed that 976 differentially expressed genes (DEGs) were identified between Fgf9VGAT and control mice. The DEGs with significantly upregulated expression were found to be involved in apoptotic and inflammatory signaling. Selected genes including Fas, Bid, Mapk11, Cxcl10, CCl2, Bik and Fos, were validated by qRT-PCR and exhibited increases in expression in Fgf9VGAT mice compared to control mice similar to those seen in the RNA-sequencing data. The expression levels of apoptosis- and inflammation-related proteins were also increased, especially those of Fas and caspase-3 pathway related proteins. Interestingly, activated ERK signaling has been observed in apoptosis and inflammatory responses induced by deleting Fgf9 in GABAergic neurons.

中文翻译：

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GABA能神经元中的FGF9敲除通过小鼠小脑中的Fas / caspase-3途径诱导凋亡和炎症。

成纤维细胞生长因子9（FGF9）是成纤维细胞生长因子家族的成员，在中枢神经系统（CNS）中广泛表达。但是，尚不清楚FGF9的工作机制如何参与小脑发育。为了解决这个问题，我们专门删除了GABA能神经元或谷氨酸能神经元中的Fgf9基因，并证明了GABA能神经元而不是谷氨酸能神经元中的Fgf9切除引起严重的共济失调。我们表明FGF9在浦肯野细胞的生存和发展中发挥了关键作用。GABA能神经元特异的FGF9敲除（Fgf9VGAT）显着影响了Purkinje细胞的存活和发育，破坏了Bergmann纤维支架的形成和小鼠颗粒神经元的迁移。RNA测序显示，在Fgf9VGAT与对照小鼠之间鉴定出976个差异表达基因（DEG）。发现表达明显上调的DEG与凋亡和炎性信号传导有关。通过qRT-PCR验证了选定的基因，包括Fas，Bid，Mapk11，Cxcl10，CCl2，Bik和Fos，与对照小鼠相比，其在Fgf9VGAT小鼠中的表达增加，与在RNA测序数据中观察到的相似。凋亡相关蛋白和炎症相关蛋白的表达水平也增加了，特别是Fas和caspase-3途径相关蛋白的表达水平也增加了。有趣的是，已观察到激活的ERK信号转导在GABA能神经元中缺失Fgf9诱导的凋亡和炎症反应中。发现表达明显上调的DEG与凋亡和炎性信号传导有关。选定的基因，包括Fas，Bid，Mapk11，Cxcl10，CCl2，Bik和Fos，已通过qRT-PCR进行了验证，与对照小鼠相比，在Fgf9VGAT小鼠中的表达增加，与在RNA测序数据中观察到的相似。凋亡相关蛋白和炎症相关蛋白的表达水平也增加了，特别是Fas和caspase-3途径相关蛋白的表达水平也增加了。有趣的是，已观察到激活的ERK信号转导在GABA能神经元中缺失Fgf9诱导的凋亡和炎症反应中。发现表达明显上调的DEG与凋亡和炎性信号传导有关。通过qRT-PCR验证了选定的基因，包括Fas，Bid，Mapk11，Cxcl10，CCl2，Bik和Fos，与对照小鼠相比，其在Fgf9VGAT小鼠中的表达增加，与在RNA测序数据中观察到的相似。凋亡相关蛋白和炎症相关蛋白的表达水平也增加了，特别是Fas和caspase-3途径相关蛋白的表达水平也增加了。有趣的是，已观察到激活的ERK信号转导在GABA能神经元中缺失Fgf9诱导的凋亡和炎症反应中。经qRT-PCR验证，与对照小鼠相比，在Fgf9VGAT小鼠中表现出增加的表达，类似于在RNA测序数据中观察到的那些。凋亡相关蛋白和炎症相关蛋白的表达水平也增加了，特别是Fas和caspase-3途径相关蛋白的表达水平也增加了。有趣的是，已观察到激活的ERK信号转导在GABA能神经元中缺失Fgf9诱导的凋亡和炎症反应中。经qRT-PCR验证，与对照小鼠相比，在Fgf9VGAT小鼠中表现出增加的表达，类似于在RNA测序数据中观察到的那些。凋亡相关蛋白和炎症相关蛋白的表达水平也增加了，特别是Fas和caspase-3途径相关蛋白的表达水平也增加了。有趣的是，已观察到激活的ERK信号转导在GABA能神经元中缺失Fgf9诱导的凋亡和炎症反应中。