CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
Genomics Proteomics Bioinformatics. 2014 Jun;12(3):111-9. doi: 10.1016/j.gpb.2014.04.004. Epub 2014 Jun 18.
Postnatal cerebral development is a complicated biological process precisely controlled by multiple genes. To understand the molecular mechanism of cerebral development, we compared dynamics of mouse cerebrum transcriptome through three developmental stages using high-throughput RNA-seq technique. Three libraries were generated from the mouse cerebrum at infancy, adolescence and adulthood, respectively. Consequently, 44,557,729 (infancy), 59,257,530 (adolescence) and 72,729,636 (adulthood) reads were produced, which were assembled into 15,344, 16,048 and 15,775 genes, respectively. We found that the overall gene expression level increased from infancy to adolescence and decreased later on upon reaching adulthood. The adolescence cerebrum has the most active gene expression, with expression of a large number of regulatory genes up-regulated and some crucial pathways activated. Transcription factor (TF) analysis suggested the similar dynamics as expression profiling, especially those TFs functioning in neurogenesis differentiation, oligodendrocyte lineage determination and circadian rhythm regulation. Moreover, our data revealed a drastic increase in myelin basic protein (MBP)-coding gene expression in adolescence and adulthood, suggesting that the brain myelin may be generated since mouse adolescence. In addition, differential gene expression analysis indicated the activation of rhythmic pathway, suggesting the function of rhythmic movement since adolescence; Furthermore, during infancy and adolescence periods, gene expression related to axonrepulsion and attraction showed the opposite trends, indicating that axon repulsion was activated after birth, while axon attraction might be activated at the embryonic stage and declined during the postnatal development. Our results from the present study may shed light on the molecular mechanism underlying the postnatal development of the mammalian cerebrum.
出生后大脑的发育是一个由多个基因精确控制的复杂生物学过程。为了了解大脑发育的分子机制,我们使用高通量 RNA-seq 技术比较了三个发育阶段的小鼠大脑转录组的动态变化。分别从小鼠大脑的婴儿期、青春期和成年期生成了三个文库。结果产生了 44557729 个(婴儿期)、59257530 个(青春期)和 72729636 个(成年期)读数,分别组装成 15344 个、16048 个和 15775 个基因。我们发现,整体基因表达水平从婴儿期到青春期增加,然后在成年后下降。青春期大脑具有最活跃的基因表达,大量的调控基因上调,一些关键途径被激活。转录因子(TF)分析表明,其动态与表达谱相似,特别是那些在神经发生分化、少突胶质细胞谱系决定和昼夜节律调节中起作用的 TF。此外,我们的数据显示,青春期和成年期髓鞘碱性蛋白(MBP)编码基因的表达急剧增加,表明大脑髓鞘可能自青春期开始产生。此外,差异基因表达分析表明节律途径的激活,表明青春期后节律运动的功能;此外,在婴儿期和青春期,与轴突排斥和吸引相关的基因表达呈现相反的趋势,表明轴突排斥在出生后被激活,而轴突吸引可能在胚胎阶段被激活,并在出生后发育过程中下降。我们目前的研究结果可能为哺乳动物大脑出生后发育的分子机制提供一些启示。