In the cerebellum, Rasgrf1 expression is limited to rostral and medial portions of the granule cell layer. Image reproduced from the Allen Brain Atlas.
Why study 1 gene when you can study 20,000? The Allen Brain Atlas characterizes the expression of nearly every gene in the mouse brain. Lein et al. describe the development of the Atlas and report patterns of gene expression that both support and challenge traditional definitions of anatomy in a recent article in Nature.
Allen Institute for Brain Science did in situ hybridization assays for each of approximately 20,000 genes in the mouse brain. They used genetically identical, inbred mice to limit individual differences and normalized in situ data to a specially created reference atlas of mouse brain anatomy to control for differences between brain sections. In situ images and 'heat maps' representing signal intensity per brain region on a colorimetric scale are freely available in the Allen Brain Atlas, where they can be searched by gene or brain structure.
Despite predictions that the brain would express a limited number of genes, the authors detected roughly 80% of all mouse genes in the brain. Approximately 70% of all genes localized to fewer than 20% of all brain cells, suggesting that most genes localized to small brain regions.
Genes uniquely or predominantly expressed in one brain region relative to all others are defined as being enriched in that region. Several brain structures, including hippocampus, thalamus, cerebellum and olfactory bulb, were highly enriched in many genes. Other structures, including the pallidum, hypothalamus, midbrain, pons and medulla, showed overlapping expression of a common set of genes and were not enriched in many genes.
The authors compared the spatial localization of genes with traditional anatomical coordinates. Large, homogeneous structures, including the striatum and cortex, overlapped with a single cluster of genes. However, structures that contain several nuclei, including the hypothalamus, pons, medulla and midbrain, had multiple overlapping clusters of genes, suggesting that brain nuclei are better predictors of gene expression than gross structures.
Gene products with restricted localization help target transgenes and gene therapies. The authors identified several genes with restricted expression. In the cerebral cortex, they found genes uniquely expressed in each cortical layer. In the hippocampus, Wfs1 , Map3k15 and Pvrl3 localized specifically to CA1, CA2 and CA3, respectively.
The authors identified several unexpected patterns of gene expression. In the hippocampus, expression of procollagen, type XV (
Col15a1
) was elevated in portions of CA3 closest to the dentate gyrus and showed progressively reduced expression in the rest of CA3, CA2 and CA1, whereas crystallin 
(
Crym
) had the reciprocal expression pattern, with elevated expression in CA1 and progressively reduced expression in CA2 and CA3. The neuropeptides gastrin-releasing peptide (
Grp
) and neuromedin b (
Nmb
) had restricted expression in the dorsal and ventral portions of the hippocampus, respectively, suggesting that these regions may be functionally distinct. In the cerebellum, the expression patterns of RAS protein-specific guanine nucleotide-releasing factor 1 (
Rasgrf1
) and encephalopsin (
Opn3
) did not correspond to known anatomical boundaries. These data suggest that region-specific gene expression may functionally define new anatomical structures in the brain.