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Genome-wide atlas of gene expression in the adult mouse brain


Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

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Figure 1: Global analysis strategy.
Figure 2: Genome-wide analysis of expression level versus percentage of expressing cells across the entire brain.
Figure 3: Representative cell-type-specific genes and corresponding molecular functions.
Figure 4: Hierarchical ranking and clustering of the most specific genes in 12 major brain regions.
Figure 5: Correlative analysis of gene expression.
Figure 6: Laminar and region-specific neocortical gene expression.
Figure 7: Heterogeneity of hippocampal gene expression.
Figure 8: Cerebellar compartments revealed by gene expression.
Figure 9: Subcellular mRNA targeting.


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This work was sponsored by the Allen Institute for Brain Science. The authors wish to thank the Allen Institute founders, P. G. Allen and J. Patton, for their vision, encouragement and support. We also wish to thank key Institute advisors, K. Dooley and S. Coliton, as well as the Scientific Advisory Board for the Atlas project, M. Tessier-Lavigne, D. Anderson, C. Dulac, R. Gibbs, S. Paul, G. Schuler, A. W. Toga and J. Takahashi, for their scientific guidance and dedication to the successful execution of the Atlas project. We would particularly like to acknowledge D. Anderson for his role in the conceptual genesis and continual refinement of Atlas goals, as well as M. Tessier-Lavigne for key scientific and organizational leadership throughout the project. We also thank C. Jennings for his critical reading of the manuscript.

Author Contributions Neuroscience Group: E.S.L. (group leader), A.B., L.C., M.P.H., M.T.M, C.L.T., T.A.Z. Informatics Group: M.J.H. (group leader), C.L.K., C.L., L.L.N., S.D.P. Production Groups: Allen Institute for Brain Science: P.E.W. (group leader), S.M.S. (group leader), R.A.J. (group leader), M.A., A.F.B., E.J.B., S.D., N.R.D., A.L.D., T.D., E.D., M.J.D., J.G.D., A.J.E., L.K.E., S.R.F., S.N.G., K.J.G., K.R.H., M.R.H., J.M.K., R.H.K., J.H.L., T.A.L., L.T.L., R.J.M., N.F.M., R.N., G.J.O., T.H.P., S.E.P., O.C.P., R.B.P., Z.L.R., H.R.R., S.A.R., J.J.R., N.R.S., K.S., N.V.S., T.S., C.R.S., S.C.S., K.A.S., N.N.S., K.-R.S., L.R.V., R.M.W., C.K.W., V.Y.W., X.F.Y.; Baylor College of Medicine: C.T. (group leader), N.A., L.C. (Li Chen), T.-M.C., A.C., R.F., A.J.L., Y.L., M.J.R., A.T., M.W., M.B.Y., B.Z.; Max Planck Institute: G.E. (group leader), A.V. Technology Group: C.N.D. (group leader), C.D.T. (group leader), A.B. (Amy Bensinger), K.S.B., M.C.C., J.C., B.E.C., T.A.D., B.J.D., T.P.F., C.F. (Cliff Frensley), D.P.J., P.T.K., R.K., A.R.L., K.D.L., J.M., B.I.S., A.J.S., M.S., R.C.Y., B.L.Y. Other: H.-W.D., B.A.F., C.F. and J.J.M., Allen Reference Atlas generation; J.G.H., data annotation; C.C.O., critical review and manuscript preparation; M.S.B., overall project leadership 2003–2004; A.R.J., overall project leadership 2004–present.

Disclaimer The Nature Publishing Group has a business collaboration with the Allen Institute for the creation and maintenance of the Neuroscience gateway (, but has no role in generating or curating the Allen Brain Atlas database content. As always, Nature Editors have been fully independent and solely responsible for the editorial content and peer review of this research article.

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Supplementary information

Supplemental Methods 1

Detailed methodologies for tissue processing, probe design and generation, data generation, and image acquisition used for the Allen Brain Atlas project (PDF 1587 kb)

Supplemental Methods 2

Detailed methodologies for informatics-based image quantification and mapping of ISH data to a common 3D coordinate system for genome-wide analysis (DOC 25603 kb)

Supplemental Methods 3

Detailed methodologies used to generate the Allen Reference Atlas (PDF 559 kb)

Supplemental Methods 4

Description of methods used for voxel-based correlation analysis (DOC 41 kb)

Supplemental Data 1

Comparison of non-isotopic in situ hybridization (ISH) data generated for the Allen Brain Atlas project to comparable radioactive ISH data from other sources (DOC 2418 kb)

Supplemental Data 2

Side-by-side image comparison of non-isotopic in situ hybridization (ISH) data generated for the Allen Brain Atlas project to comparable radioactive ISH data. Accompanies Supplemental Data 1 (PDF 19230 kb)

Supplemental Data 3

Control data demonstrating the reproducibility of the ABA ISH platform across conditions and across the duration of the ABA project (PDF 4775 kb)

Supplemental Data 4

Comparison of expression patterns of the ligand-gated ion channel family to available literature and other data sources, as well as methodology for fine-detailed expert annotation of the ligand-gated ion channel family in the neocortex (DOC 412 kb)

Supplemental Data 5

Detailed expert annotation of the complete ligand-gated ion channel family in layers of the neocortex. Accompanies Supplemental Data 4 (XLS 44 kb)

Supplemental Figure 1

Genome-wide analysis of expression level vs. percentage of expressing cells in 12 major brain regions (JPG 840 kb)

Supplementary Table 1

Genes enriched in major cell populations in the brain (neurons, oligodendrocytes, astrocytes, and choroid plexus cells) identified through correlation-based searches seeded with cell-type specific gene expression patterns. Also included are genes with apparent ubiquity as well as genes that do not have detectable expression in the brain (XLS 184 kb)

Supplemental Table 2

Gene Ontology (GO) categories over-represented in genes enriched in major neural cell types and in genes that are either apparently ubiquitous or not expressed. Accompanies Supplemental Table 1 (XLS 612 kb)

Supplemental Table 3

Genes identified as the most specific for each of 12 different major brain regions (XLS 198 kb)

Supplemental Table 4

Genes displaying mRNA targeting to dendrites (neurons) or processes (non-neuronal cells) (XLS 37 kb)

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Lein, E., Hawrylycz, M., Ao, N. et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168–176 (2007).

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