Correlation between gene functions and developmental expression patterns in the mouse cerebellum

Quantitative changes of 419 gene transcripts during postnatal mouse cerebellar development were accurately determined with a novel polymerase chain reaction (PCR)‐based technique. About 70% of the genes showed differences in expression levels, and the magnitude of difference was relatively small. By hierarchic cluster analysis of developmental expression patterns, the genes were categorized into 19 clusters, which were subsequently assembled into four major groups: group 1, with elevation of gene expression throughout the time course; group 2, with relatively unchanged levels; group 3, with transiently high expression at ∼ 12 days; and group 4, with highest expression at ∼ 4 days. Genes related to brain functions were segregated into several clusters of group 1 and group 3: the same clusters in which cerebellum‐specific genes were also segregated. Genes for protein synthesis belonged to group 4. Genes with housekeeping functions belonged to group 2. Western blotting analysis of representative protein products of each group revealed correlation with the mRNA level for those belonging to group 1 and group 4, but not necessarily in the other groups. The close correlation of algorithmically categorized temporal expression patterns of genes with their functions will be useful for estimating the functions of thousands of novel genes.

[1]  Michael Ruogu Zhang,et al.  Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. , 1998, Molecular biology of the cell.

[2]  R. Reynolds,et al.  Development of macroglial cells in rat cerebellum. I. Use of antibodies to follow earlyin vivo development and migration of oligodendrocytes , 1988, Journal of neurocytology.

[3]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[4]  Kikuya Kato,et al.  Adaptor-tagged competitive PCR: a novel method for measuring relative gene expression. , 1997, Nucleic acids research.

[5]  C. Finch,et al.  Sequence complexity of polyadenylated RNA obtained from rat brain regions and cultured rat cells of neural origin. , 1978, Biochemistry.

[6]  K. Kato,et al.  Description of the entire mRNA population by a 3' end cDNA fragment generated by class IIS restriction enzymes. , 1995, Nucleic acids research.

[7]  Ji Huang,et al.  [Serial analysis of gene expression]. , 2002, Yi chuan = Hereditas.

[8]  R. Williams,et al.  The control of neuron number. , 1988, Annual review of neuroscience.

[9]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[10]  D. Botstein,et al.  The transcriptional program of sporulation in budding yeast. , 1998, Science.

[11]  J. Bantle,et al.  Complexity and characterization of polyadenylated RNA in the mouse brain , 1976, Cell.

[12]  A. Belyavsky,et al.  Identification of differentially expressed genes by restriction endonuclease-based gene expression fingerprinting. , 1995, Nucleic acids research.

[13]  D. Lockhart,et al.  Expression monitoring by hybridization to high-density oligonucleotide arrays , 1996, Nature Biotechnology.

[14]  H. Charles Romesburg,et al.  Cluster analysis for researchers , 1984 .

[15]  Kousaku Okubo,et al.  Large scale cDNA sequencing for analysis of quantitative and qualitative aspects of gene expression , 1992, Nature Genetics.

[16]  Dan Goldowitz,et al.  The cells and molecules that make a cerebellum , 1998, Trends in Neurosciences.

[17]  K Matsubara,et al.  Gene expression in mouse cerebellum during its development. , 2000, Gene.

[18]  J. Altman,et al.  Postnatal development of the cerebellar cortex in the rat. I. The external germinal layer and the transitional molecular layer , 1972, The Journal of comparative neurology.

[19]  A. Winfree,et al.  Postnatal development of the cerebellar cortex in the rat: V. Spatial organization of Purkinje cell perikarya , 1977, The Journal of comparative neurology.

[20]  J. Barker,et al.  Large-scale temporal gene expression mapping of central nervous system development. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[21]  K. Livak,et al.  Oligonucleotides with fluorescent dyes at opposite ends provide a quenched probe system useful for detecting PCR product and nucleic acid hybridization. , 1995, PCR methods and applications.

[22]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.