Avet-Rochex Amélie, Maierbrugger Katja T, Bateman Joseph M
Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London SE1 1UL, UK.
Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London SE1 1UL, UK.
Gene Expr Patterns. 2014 Sep;16(1):61-8. doi: 10.1016/j.gep.2014.09.001. Epub 2014 Sep 10.
Glial cells constitute a large proportion of the central nervous system (CNS) and are critical for the correct development and function of the adult CNS. Recent studies have shown that specific subtypes of glia are generated through the proliferation of differentiated glial cells in both the developing invertebrate and vertebrate nervous systems. However, the factors that regulate glial proliferation in specific glial subtypes are poorly understood. To address this we have performed global gene expression analysis of Drosophila post-embryonic CNS tissue enriched in glial cells, through glial specific overexpression of either the FGF or insulin receptor. Analysis of the differentially regulated genes in these tissues shows that the expression of known glial genes is significantly increased in both cases. Conversely, the expression of neuronal genes is significantly decreased. FGF and insulin signalling drive the expression of overlapping sets of genes in glial cells that then activate proliferation. We then used these data to identify novel transcription factors that are expressed in glia in the brain. We show that two of the transcription factors identified in the glial enriched gene expression profiles, foxO and tramtrack69, have novel roles in regulating the proliferation of cortex and perineurial glia. These studies provide new insight into the genes and molecular pathways that regulate the proliferation of specific glial subtypes in the Drosophila post-embryonic brain.
神经胶质细胞在中枢神经系统(CNS)中占很大比例,对成年中枢神经系统的正确发育和功能至关重要。最近的研究表明,在发育中的无脊椎动物和脊椎动物神经系统中,特定亚型的神经胶质细胞是通过已分化的神经胶质细胞增殖产生的。然而,调节特定神经胶质细胞亚型增殖的因素却知之甚少。为了解决这个问题,我们通过在果蝇胚胎后中枢神经系统组织中特异性过表达成纤维细胞生长因子(FGF)或胰岛素受体,对富含神经胶质细胞的组织进行了全基因组表达分析。对这些组织中差异调节基因的分析表明,在这两种情况下,已知神经胶质细胞基因的表达均显著增加。相反,神经元基因的表达则显著下降。FGF和胰岛素信号传导驱动神经胶质细胞中重叠基因集的表达,进而激活细胞增殖。然后,我们利用这些数据鉴定出在大脑神经胶质细胞中表达的新型转录因子。我们发现,在富含神经胶质细胞的基因表达谱中鉴定出的两种转录因子,即叉头框蛋白O(foxO)和轨道蛋白69(tramtrack69),在调节皮质和神经束膜神经胶质细胞的增殖中具有新的作用。这些研究为调节果蝇胚胎后大脑中特定神经胶质细胞亚型增殖的基因和分子途径提供了新的见解。