Badenhorst P
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
Development. 2001 Oct;128(20):4093-101. doi: 10.1242/dev.128.20.4093.
Neurons and glia are often derived from common multipotent stem cells. In Drosophila, neural identity appears to be the default fate of these precursors. Stem cells that generate either neurons or glia transiently express neural stem cell-specific markers. Further development as glia requires the activation of glial-specific regulators. However, this must be accompanied by simultaneous repression of the alternate neural fate. I show that the Drosophila transcriptional repressor Tramtrack is a key repressor of neuronal fates. It is expressed at high levels in all mature glia of the embryonic central nervous system. Analysis of the temporal profile of Tramtrack expression in glia shows that it follows that of existing glial markers. When expressed ectopically before neural stem cell formation, Tramtrack represses the neural stem cell-specific genes asense and deadpan. Surprisingly, Tramtrack protein levels oscillate in a cell cycle-dependent manner in proliferating glia, with expression dropping before replication, but re-initiating after S phase. Overexpression of Tramtrack blocks glial development by inhibiting S-phase and repressing expression of the S-phase cyclin, cyclin E. Conversely, in tramtrack mutant embryos, glia are disrupted and undergo additional rounds of replication. I propose that Tramtrack ensures stable mature glial identity by both repressing neuroblast-specific genes and controlling glial cell proliferation.
神经元和神经胶质细胞通常源自共同的多能干细胞。在果蝇中,神经特性似乎是这些前体细胞的默认命运。产生神经元或神经胶质细胞的干细胞会短暂表达神经干细胞特异性标志物。向神经胶质细胞的进一步发育需要激活胶质细胞特异性调节因子。然而,这必须同时伴随着对另一种神经命运的抑制。我发现果蝇转录抑制因子Tramtrack是神经元命运的关键抑制因子。它在胚胎中枢神经系统的所有成熟神经胶质细胞中高水平表达。对神经胶质细胞中Tramtrack表达的时间模式分析表明,它与现有的神经胶质细胞标志物的表达模式一致。当在神经干细胞形成之前异位表达时,Tramtrack会抑制神经干细胞特异性基因asense和deadpan。令人惊讶的是,在增殖的神经胶质细胞中,Tramtrack蛋白水平以细胞周期依赖性方式振荡,在复制前表达下降,但在S期后重新开始表达。Tramtrack的过表达通过抑制S期和抑制S期细胞周期蛋白cyclin E的表达来阻断神经胶质细胞的发育。相反,在tramtrack突变体胚胎中,神经胶质细胞被破坏并经历额外的复制轮次。我认为Tramtrack通过抑制神经母细胞特异性基因和控制神经胶质细胞增殖来确保稳定的成熟神经胶质细胞特性。