Genome-wide analyses of genes predominantly expressed in the mouse neocortex

哺乳动物大脑新皮质占据了大脑皮层最大的区域，其细胞结构由六层(I-VI)组成。许多神经系统疾病，包括精神疾病，都是由新皮质功能障碍引起的。尽管新大脑皮层具有重要的功能，但通过包括全基因组技术在内的分子生物学方法，它实际上是一个未被探索的区域。利用微阵列的全球筛选，结合系统的原位杂交，已经为我们提供了几个候选基因，这些基因主要在小鼠的新皮质中表达。其中，锌指型转录因子FEZ被进一步详细分析。到目前为止，还没有其他基因在新大脑皮层中具有最强的特异性表达。用双色原位杂交方法显示FEZ主要表达于大脑皮质V层，而不是GABA神经元，而是大脑皮质的投射神经元锥体神经元。通过我们的系统分析确定的分子不仅对于分子理解新大脑皮层的发育和功能，而且对于在基因操纵的动物以及条件表达系统中使用它们的启动子都是非常有价值的。

The mammalian cerebral neocortex occupies the largest area of the cerebral cortex and is cytoarchitectually composed of six layers (I-VI). Many of neurological diseases including the mental illnesses are due to the dysfunction of the neocortex. In spite of its functional importance, the neocortex is virtually an unexplored region by approaches of molecular biology including the genome-wide technology. The global screening using microarrays, combined with the systematic in situ hybridization, has provided us with several candidate genes that are expressed predominantly in the mouse neocortex. Among them, Fez, a zinc finger type transcription factor, was analyzed in further detail. No other genes in the neocortex have been known so far to have their expression the strongest in terms of specificity. Using two color in situ hybridization, we have shown that Fez is mainly expressed in the cortical layer V, not in the GABA neurons but in the pyramidal neurons, the projection neurons of the cerebral cortex. Molecules identified by our systematic analyses would be invaluable not only for molecular understanding of the development and function of the neocortex but also for the use of their promoters in the gene-manipulated animals as well as in conditional expression systems.