Ozen Ilknur, Galichet Christophe, Watts Colin, Parras Carlos, Guillemot François, Raineteau Olivier
Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge, UK.
Eur J Neurosci. 2007 May;25(9):2591-603. doi: 10.1111/j.1460-9568.2007.05541.x. Epub 2007 Apr 27.
Little is known of the transcription factors expressed by adult neural progenitors produced in the hippocampal neurogenic niche. Here, we study the expression of the proneural basic helix-loop-helix (bHLH) transcription factor Neurogenin-2 (Ngn2) in the adult hippocampus. We have characterized the pattern of expression of Ngn2 in the adult hippocampus using immunostaining for Ngn2 protein and a Ngn2-green fluorescent protein (GFP) reporter mouse strain. A significant proportion of Ngn2-expressing cells were mitotically active. Ngn2-GFP expression was restricted to the subgranular zone and declined with age. Neuronal markers were used to determine the phenotype of Ngn2-expressing cells. The vast majority of Ngn2-GFP-positive cells expressed the immature neuronal markers, doublecortin (DCX) and polysialic acid-neural cell adhesion molecule (PSA-NCAM). Finally, the pattern of Ngn2 expression was studied following seizure induction. Our data show an increase in neurogenesis, detected in these animals by bromodeoxyuridine (BrdU) and DCX staining that was contemporaneous with a marked increase in Ngn2-GFP-expression. Taken together, our results show that Ngn2-GFP represents a specific marker for neurogenesis and its modulation in the adult hippocampus. Ngn2 transient expression in proliferating neuronal progenitors supports the idea that it plays a significant role in adult neurogenesis.
关于海马神经发生微环境中产生的成年神经祖细胞所表达的转录因子,我们了解得很少。在此,我们研究神经源性碱性螺旋-环-螺旋(bHLH)转录因子神经生成素-2(Ngn2)在成年海马体中的表达。我们利用针对Ngn2蛋白的免疫染色和一种Ngn2-绿色荧光蛋白(GFP)报告基因小鼠品系,对成年海马体中Ngn2的表达模式进行了表征。相当一部分表达Ngn2的细胞具有有丝分裂活性。Ngn2-GFP的表达局限于颗粒下区,并随年龄增长而下降。我们使用神经元标志物来确定表达Ngn2的细胞的表型。绝大多数Ngn2-GFP阳性细胞表达未成熟神经元标志物,双皮质素(DCX)和多唾液酸神经细胞黏附分子(PSA-NCAM)。最后,我们在癫痫诱导后研究了Ngn2的表达模式。我们的数据显示,通过溴脱氧尿苷(BrdU)和DCX染色在这些动物中检测到神经发生增加,这与Ngn2-GFP表达的显著增加同时发生。综上所述,我们的结果表明,Ngn2-GFP代表成年海马体中神经发生及其调节的一种特异性标志物。Ngn2在增殖的神经元祖细胞中的短暂表达支持了它在成年神经发生中起重要作用的观点。