Multi-stage analysis of differential gene expression in BALB/C mouse liver development by high-density microarrays.

The development of a complex organ such as the liver relies on precise temporal and spatial gene expression patterns during ontogenesis. The unique adult phenotype is a result of a cascade of transcriptional events that finally trigger gene expression in a liver-specific fashion. Development in mice starts at embryonic stage E8.5-9.5 with the expression of several genes typically associated with liver tissue. While the role of some genes and their expression is well studied, little is known about the complex expression pattern changes during embryonic and fetal liver development. High-density oligonucleotide microarrays, which allow simultaneous expression analysis of 12,488 mouse mRNA transcripts and EST sequences, were used to study the gene expression profiles in day 7.5 embryonic tissue, in micro-dissected fetal liver tissue from day 11.5 and day 13.5 embryos, and in adult liver. In pairwise comparisons of all stages, a total of 4242 distinct genes or ESTs were found to be differentially regulated. Cross-comparisons of data from all stages detected the highest number of differentially regulated genes in E11.5 fetal liver tissue versus adult liver (3063 genes) and the lowest number in E11.5 versus E13.5 fetal liver tissue (517 genes). Using adult liver as reference tissue, 212 genes were regulated exclusively in E7.5 embryonic tissue, 303 genes in E11.5 and 198 in E13.5 fetal liver tissue. Expression profiles of the 31 genes with significant regulation at all stages as well as of a number of known developmentally regulated genes were compared with published results and interpreted. The gene expression profiles detected by microarray hybridization were independently confirmed for selected genes by quantitative RT-PCR. Our data presented here suggest that a relatively small number of stage-specific genes exist, which may be of particular importance for liver development, growth and differentiation. Furthermore, the microarray approach led to the identification of a number of genes, which have not yet been associated with liver organogenesis and maturation.