A high-resolution anatomical atlas of the transcriptome in the mouse embryo.

Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.

An analysis of expression patterns of genes encoding proteins with catalytic activities.

BACKGROUND: In situ hybridization (ISH) is a powerful method for visualizing gene expression patterns at the organismal level with cellular resolution. When automated, it is capable of determining the expression of a large number of genes. RESULTS: The expression patterns of 662 genes that encode enzymes were determined by ISH in the mid-gestation mouse embryo, a stage that models the complexity of the adult organism. Forty-five percent of transcripts encoding metabolic enzymes (n = 297) showed a regional expression pattern. A similar percentage was found for the 190 kinases that were also analyzed. Many mRNAs encoding glycolytic and TCA cycle enzymes exhibited a characteristic expression pattern. The annotated expression patterns were deposited on the Genepaint database and are retrievable by user-defined queries including gene name and sites of expression. CONCLUSION: The 662 expression patterns discussed here comprised gene products with activities associated with catalysis. Preliminary analysis of these data revealed that a significant number of genes encoding housekeeping functions such as biosynthesis and catabolism were expressed regionally, so they could be used as tissue-specific gene markers. We found no difference in tissue specificity between mRNAs encoding housekeeping functions and those encoding components of signal transduction pathways, as exemplified by the kinases.