Transcription profiling of twenty four mouse neural tissues and ten body regions from five inbred strains to build a gene expression-based brain map

The current model to explain the organization of the mammalian nervous system is based on studies of anatomy, embryology, and evolution. To further investigate the molecular organization of the adult mammalian brain, we have built a gene expression-based brain map. We measured gene expression patterns for 24 neural tissues covering the mouse central nervous system and found, surprisingly, that the adult brain bears a transcriptional imprint" consistent with both embryological origins and classic evolutionary relationships. Embryonic cellular position along the anterior-posterior axis of the neural tube was shown to be closely associated with, and possibly a determinant of, the gene expression patterns in adult structures. We also observed a significant number of embryonic patterning and homeobox genes with region-specific expression in the adult nervous system. The relationships between global expression patterns for different anatomical regions and the nature of the observed region-specific genes suggest that the adult brain retains a degree of overall gene expression established during embryogenesis that is important for regional specificity and the functional relationships between regions in the adult. The complete collection of extensively annotated gene expression data along with data mining and visualization tools have been made available on a publicly accessible web site (www.barlow-lockhartbrainmapnimhgrant.org). Experiment Overall Design: Large amount of high-quality, quantitative gene expression data obtained for 24 neural tissues from 3 strains of inbred mice and and 10 body tissues from 5 strains of inbred mice.当前解释哺乳动物神经系统组织架构的主流模型，基于解剖学、胚胎学及进化研究构建。为进一步探究成年哺乳动物大脑的分子组织模式，本研究构建了基于基因表达谱的大脑图谱。我们针对覆盖小鼠中枢神经系统的24种神经组织开展了基因表达谱检测，意外发现成年大脑存在一种转录印记（transcriptional imprint），该印记同时契合胚胎起源与经典进化关联。研究显示，神经管前后轴上的胚胎细胞位置，与成年组织的基因表达谱紧密相关，甚至可能是其决定性因素。我们还观察到，大量参与胚胎模式建成的基因以及同源框（homeobox）基因，在成年神经系统中呈现区域特异性表达。不同解剖区域的全局基因表达模式，与所观测到的区域特异性基因的特性之间的关联表明，成年大脑保留了部分在胚胎发生阶段确立的整体基因表达特征，这些特征对于成年大脑的区域特异性以及区域间功能关联至关重要。全套经过详尽注释的基因表达数据，搭配数据挖掘与可视化工具，已通过公开可访问的网站（www.barlow-lockhartbrainmapnimhgrant.org）对外发布。实验整体设计：本研究获取了来自3个近交品系小鼠的24种神经组织，以及5个近交品系小鼠的10种躯体组织的海量高质量定量基因表达数据。