Lim Chun Ren, Fukakusa Ako, Matsubara Kenichi
DNA Chip Research Inc. 1-1-43 Suehirocho, Tsurumi, Yokohama 230-0045, Japan.
Gene. 2004 May 26;333:3-13. doi: 10.1016/j.gene.2004.02.026.
The cerebellum serves as a model system for developmental studies of the mammalian nervous system. Classical analysis of individual genes is insufficient to address the complex regulatory circuits underlying the developmental process. In this study, the postnatal cerebellar development of mice aged 2, 4, 8, 12, 16, 21 and 42 days old was studied using a microarray spotted with 5494 cDNA clones collected from the cerebellum and the cerebrum of C57BL/6J mice. We were able to cluster the expression patterns into four groups and each was highly correlated with gene function. Housekeeping genes are in a cluster in which the expression pattern peaks at the neonatal stage, while genes related to brain function peak at the adult stage. The other two clusters, characterized by transiently upregulated or downregulated expression during days 8-16, contain genes with different functions, most notably related to cell differentiation and cell cycle progression. Based on this categorization and on motif scanning, we were able to assign hypothetical functions to functionally undetermined genes. The result indicates that expression profiling is an efficient method for generation of new hypotheses for the developmental study of the cerebellum. When combined with other studies such as pharmacology etc., data generated in this study may have application in the elucidation of genetic networks underlying developmental disorder.
小脑是哺乳动物神经系统发育研究的一个模型系统。对单个基因进行经典分析不足以阐明发育过程背后复杂的调控回路。在本研究中,使用点有从C57BL/6J小鼠的小脑和大脑收集的5494个cDNA克隆的微阵列,研究了2、4、8、12、16、21和42日龄小鼠出生后小脑的发育情况。我们能够将表达模式聚类为四组,每组都与基因功能高度相关。管家基因聚在一组,其表达模式在新生儿期达到峰值,而与脑功能相关的基因在成年期达到峰值。另外两组的特征是在第8至16天期间表达短暂上调或下调,包含具有不同功能的基因,最显著的是与细胞分化和细胞周期进程相关的基因。基于这种分类和基序扫描,我们能够为功能未确定的基因赋予假设功能。结果表明,表达谱分析是为小脑发育研究生成新假设的一种有效方法。当与其他研究如药理学等结合时,本研究产生的数据可能在阐明发育障碍背后的遗传网络方面有应用价值。