Abstract
The Allen Brain Atlas, a Web-based, genome-wide atlas of gene expression in the adult mouse brain, was an experiment on a massive scale. The development of the atlas faced a combination of great technical challenges and a non-traditional open research model, and it encountered many hurdles on the path to completion and community adoption. Having overcome these challenges, it is now a fundamental tool for neuroscientists worldwide and has set the stage for the creation of other similar open resources. Nevertheless, there are many untapped opportunities for exploration.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Tessier-Lavigne, M. & Stryer, L. Setting priorities for molecular neuroanatomy in the postgenomic era. NIH NIDA [online], (2002).
Heintz, N. Gene expression nervous system atlas (GENSAT). Nature Neurosci. 7, 483 (2004).
Geschwind, D. GENSAT: a genomic resource for neuroscience research. Lancet Neurol. 3, 82 (2004).
Gong, S. et al. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425, 917–925 (2003).
Tecan. The GenePaint System. Mol. Biotechnol. 25, 103–104 (2003).
Mamounas, L., Gubitz, A. K. & Talley, N. NIH blueprint for neuroscience research: GENSAT. NIH [online], (2008).
Burris, J., Cook-Deegan, R. & Alberts, B. The Human Genome Project after a decade: policy issues. Nature Genet. 20, 333–335 (1998).
Collins, F. S., Morgan, M. & Patrinos, A. The Human Genome Project: lessons from large-scale biology. Science 300, 286–290 (2003).
Allen Institute for Brain Science. ISH platform controls. Allen Brain Atlas [online], (2006).
Allen Institute for Brain Science. Cross platform validation. Allen Brain Atlas [online], (2006).
Allen Institute for Brain Science. Informatics data processing. Allen Brain Atlas [online], (2006).
Allen Institute for Brain Science. Data production processes. Allen Brain Atlas [online], (2006).
Allen Institute for Brain Science. NeuroBlast: user guide. Allen Brain Atlas [online], (2007).
Allen Institute for Brain Science. AGEA user guide. Allen Brain Atlas [online], (2007).
Lein, E. S. et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168–176 (2007).
Ng, L. L. et al. Neuroinformatics for genome-wide 3D gene expression mapping in the mouse brain. IEEE/ACM Trans Comput. Biol. Bioinform. 4, 382–393 (2007).
Lau, C. et al. Exploration and visualization of gene expression with neuroanatomy in the adult mouse brain. BMC Bioinformatics 9, 153–163 (2008).
Ng, L. et al. An anatomic gene expression atlas of the adult mouse brain. Nature Neurosci. 12, 356–362 (2009).
Lee, C. K. et al. Quantitative methods for genome-scale analysis of in situ hybridization and correlation with microarray data. Genome Biol. 9, R23 (2008).
Gosso, F. M. et al. Exploring the functional role of the CHRM2 gene in human cognition: results from a dense genotyping and brain expression study. BMC Med. Genet. 8, 66 (2007).
Hougaard, D. M., Hansen, H. & Larsson, L. I. Non-radioactive in situ hybridization for mRNA with emphasis on the use of oligodeoxynucleotide probes. Histochem. Cell Biol. 108, 335–344 (1997).
Higo, N., Oishi, T., Yamashita, A., Matsuda, K. & Hayashi, M. Quantitative non-radioactive in situ hybridization study of GAP-43 and SCG10 mRNAs in the cerebral cortex of adult and infant macaque monkeys. Cereb. Cortex 9, 317–331 (1999).
Bello, M. et al. Hybrid segmentation framework for tissue images containing gene expression data. Med. Image Comput. Comput. Assist. Interv. Int. Conf. Med. Image Comput. Comput. Assist. Interv. 8, 254–261 (2005).
Carson, J. P. et al. A digital atlas to characterize the mouse brain transcriptome. PLoS Comput.Biol. 1, e41 (2005).
Sandberg, R. et al. Regional and strain-specific gene expression mapping in the adult mouse brain. Proc. Natl Acad. Sci. USA 97, 11038–11043 (2000).
Heimel, J. A., Hermans, J. M., Sommeijer, J. P. & Levelt, C. N. Genetic control of experience-dependent plasticity in the visual cortex. Genes Brain Behav. 7, 915–923 (2008).
Allen Institute for Brain Science. Comparison of the top 1000 genes. Allen Brain Atlas [online], (2007).
Mi, H., Guo, N., Kejariwal, A. & Thomas, P. D. PANTHER version 6: protein sequence and function evolution data with expanded representation of biological pathways. Nucleic Acids Res. 35, D1247–D1252 (2007).
McHugh, P. C. et al. Downregulation of Ccnd1 and Hes6 in rat hippocampus after chronic exposure to the antidepressant paroxetine. Acta Neuropsychiatrica 20, 307–313 (2008).
Ball-Rosen, C. et al. Identification of histidine-rich glycoprotein, a potential autoantigen, in human and rat brain preparations. Ann. NY Acad. Sci. 1109, 473–483 (2007).
Greene, J. G., Borges, K. & Dingledine, R. Quantitative transcriptional neuroanatomy of the rat hippocampus: evidence for wide-ranging, pathway-specific heterogeneity among three principal cell layers. Hippocampus 19, 253–264 (2009).
Sakakibara, S. et al. Developmental and spatial expression pattern of alpha-taxilin in the rat central nervous system. J. Comp. Neurol. 511, 65–80 (2008).
Benoist, M. et al. Distribution of zinedin in the rat brain. J. Neurochem. 106, 969–977 (2008).
Oldham, M. C. et al. Functional organization of the transcriptome in human brain. Nature Neurosci. 11, 1271–1282 (2008).
Ernst, C. et al. Confirmation of region-specific patterns of gene expression in the human brain. Neurogenetics 8, 219–224 (2007).
Von Stetina, S. E. et al. Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system. Genome Biol. 8, R135 (2007).
Mecklenburg, K. L. Drosophila retinophilin contains MORN repeats and is conserved in humans. Mol. Genet. Genomics 277, 481–489 (2007).
Chizhikov, V. V. et al. Cilia proteins control cerebellar morphogenesis by promoting expansion of the granule progenitor pool. J. Neurosci. 27, 9780–9789 (2007).
Cahoy, J. D. et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci. 28, 264–278 (2008).
Tabakoff, B. et al. The genomic determinants of alcohol preference in mice. Mamm. Genome 19, 352–365 (2008).
Kelai, S. et al. Nrxn3 upregulation in the globus pallidus of mice developing cocaine addiction. Neuroreport 19, 751–755 (2008).
Andrade, N. et al. ApoER2/VLDL receptor and Dab1 in the rostral migratory stream function in postnatal neuronal migration independently of Reelin. Proc. Natl Acad. Sci. USA 104, 8508–8513 (2007).
Satoh, J. et al. Protein microarray analysis identifies human cellular prion protein interactors. Neuropathol. Appl. Neurobiol. 35, 16–35 (2009).
Lim, J. et al. Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1. Nature 452, 713–718 (2008).
Mozhui, K. et al. Dissection of a QTL hotspot on mouse distal chromosome 1 that modulates neurobehavioral phenotypes and gene expression. PLoS Genet. 4, e1000260 (2008).
Alavian, K. N. & Simon, H. H. Linkage of cDNA expression profiles of mesencephalic dopaminergic neurons to a genome-wide in situ hybridization database. Mol. Neurodegener. 4, 6 (2009).
Papassotiropoulos, A. et al. Common Kibra alleles are associated with human memory performance. Science 314, 475–478 (2006).
Gerhard, D. S. et al. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 14, 2121–2127 (2004).
Carninci, P. et al. The transcriptional landscape of the mammalian genome. Science 309, 1559–1563 (2005).
Sunkin, S. M. & Hohmann, J. G. Insights from spatially mapped gene expression in the mouse brain. Hum. Mol. Genet. 16, R209–R219 (2007).
Ramos, R. L., Smith, P. T. & Brumberg, J. C. Novel in silico method for teaching cytoarchitecture, cellular diversity, and gene expression in the mammalian brain. Journal of Undergraduate Neuroscience Education 6, A8–A13 (2007).
Jenks, B. G. A self-study tutorial using the Allen Brain Explorer and Brain Atlas to teach concepts of mammalian neuroanatomy and brain function. Journal of Undergraduate Neuroscience Education 8, A21–A25 (2009).
Davis, F. P. & Eddy, S. R. A tool for identification of genes expressed in patterns of interest using the Allen Brain Atlas. Bioinformatics 25, 1647–1654 (2009).
Lichtman, J. W. & Sanes, J. R. Ome sweet ome: what can the genome tell us about the connectome? Curr. Opin. Neurobiol. 18, 346–353 (2008).
Jagalur, M., Pal, C., Learned-Miller, E., Zoeller, R. T. & Kulp, D. Analyzing in situ gene expression in the mouse brain with image registration, feature extraction and block clustering. BMC Bioinformatics 8 (Suppl. 10), S5 (2007).
Haitina, T. et al. Expression profile of the entire family of Adhesion G protein-coupled receptors in mouse and rat. BMC Neurosci. 9, 43 (2008).
D'Souza, C. A. et al. Identification of a set of genes showing regionally enriched expression in the mouse brain. BMC Neurosci. 9, 66 (2008).
Olszewski, P. K., Cedernaes, J., Olsson, F., Levine, A. S. & Schioth, H. B. Analysis of the network of feeding neuroregulators using the Allen Brain Atlas. Neurosci. Biobehav. Rev. 32, 945–956 (2008).
Ramos, R. L. et al. Cytoarchitecture and transcriptional profiles of neocortical malformations in inbred mice. Cereb. Cortex 18, 2614–2628 (2008).
Loerch, P. M. et al. Evolution of the aging brain transcriptome and synaptic regulation. PLoS ONE 3, e3329 (2008).
Sun, Y. G. et al. Involvement of P311 in the affective, but not in the sensory component of pain. Mol. Pain 4, 23 (2008).
Kim, D. S. et al. Identification of molecular markers of bipolar cells in the murine retina. J. Comp. Neurol. 507, 1795–1810 (2008).
Zhang, Y. et al. Comparative analysis of selenocysteine machinery and selenoproteome gene expression in mouse brain identifies neurons as key functional sites of selenium in mammals. J. Biol. Chem. 283, 2427–2438 (2008).
Uhl, G. R. et al. Molecular genetics of addiction and related heritable phenotypes: genome-wide association approaches identify “connectivity constellation” and drug target genes with pleiotropic effects. Ann. NY Acad. Sci. 1141, 318–381 (2008).
Lee, A. M. & Messing, R. O. Protein kinases and addiction. Ann. NY Acad. Sci. 1141, 22–57 (2008).
Hishimoto, A. et al. Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms. Hum. Mol. Genet. 16, 2880–2891 (2007).
Hu, W. et al. Genomic insights into acute alcohol tolerance. J. Pharmacol. Exp. Ther. 326, 792–800 (2008).
McKay, B. E., Placzek, A. N. & Dani, J. A. Regulation of synaptic transmission and plasticity by neuronal nicotinic acetylcholine receptors. Biochem. Pharmacol. 74, 1120–1133 (2007).
Inestrosa, N. C. & Toledo, E. M. The role of Wnt signaling in neuronal dysfunction in Alzheimer's disease. Mol. Neurodegener. 3, 9 (2008).
Reiman, E. M. et al. GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers. Neuron 54, 713–720 (2007).
Muhammad, A. et al. Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Aβ accumulation. Proc. Natl Acad. Sci. USA 105, 7327–7332 (2008).
Small, S. A. Retromer sorting: a pathogenic pathway in late-onset Alzheimer disease. Arch. Neurol. 65, 323–328 (2008).
Hamamichi, S. et al. Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model. Proc. Natl Acad. Sci. USA 105, 728–733 (2008).
Park, J. W., Park, E. S., Choi, E. N., Park, H. Y. & Jung, S. C. Altered brain gene expression profiles associated with the pathogenesis of phenylketonuria in a mouse model. Clin. Chim. Acta 401, 90–99 (2009).
Saxe, J. P. et al. A phenotypic small-molecule screen identifies an orphan ligand-receptor pair that regulates neural stem cell differentiation. Chem. Biol. 14, 1019–1030 (2007).
Belichenko, N. P., Belichenko, P. V., Li, H. H., Mobley, W. C. & Francke, U. Comparative study of brain morphology in Mecp2 mutant mouse models of Rett syndrome. J. Comp. Neurol. 508, 184–195 (2008).
Liu, C., Wang, Y., Smallwood, P. M. & Nathans, J. An essential role for Frizzled5 in neuronal survival in the parafascicular nucleus of the thalamus. J. Neurosci. 28, 5641–5653 (2008).
Sandoz, G. et al. Mtap2 is a constituent of the protein network that regulates twik-related K+ channel expression and trafficking. J. Neurosci. 28, 8545–8552 (2008).
Sakurai, K. & Osumi, N. The neurogenesis-controlling factor, Pax6, inhibits proliferation and promotes maturation in murine astrocytes. J. Neurosci. 28, 4604–4612 (2008).
Gatchel, J. R. et al. The insulin-like growth factor pathway is altered in spinocerebellar ataxia type 1 and type 7. Proc. Natl Acad. Sci. USA 105, 1291–1296 (2008).
Glazov, E. A., McWilliam, S., Barris, W. C. & Dalrymple, B. P. Origin, evolution, and biological role of miRNA cluster in DLK-DIO3 genomic region in placental mammals. Mol. Biol. Evol. 25, 939–948 (2008).
Negrete, O. A., Chu, D., Aguilar, H. C. & Lee, B. Single amino acid changes in the Nipah and Hendra virus attachment glycoproteins distinguish ephrinB2 from ephrinB3 usage. J. Virol. 81, 10804–10814 (2007).
Letellier, M., Willson, M. L., Gautheron, V., Mariani, J. & Lohof, A. M. Normal adult climbing fiber monoinnervation of cerebellar Purkinje cells in mice lacking MHC class I molecules. Dev. Neurobiol. 68, 997–1006 (2008).
Rodgers, B. D. & Garikipati, D. K. Clinical, agricultural, and evolutionary biology of myostatin: a comparative review. Endocr. Rev. 29, 513–534 (2008).
Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990).
Ng, L. et al. NeuroBlast: a 3D spatial homology search tool for gene expression. BMC Neurosci. 8, 11 (2007).
Dong, H. W. The Allen Reference Atlas: A Digital Color Brain Atlas of the C57BL/6J Male Mouse (Wiley, Hoboken, New Jersey, 2008).
Acknowledgements
This work was sponsored by the Allen Institute for Brain Science. The authors wish to thank the Allen Institute founders, Paul G. Allen and Jody Allen, for their vision, encouragement and support.
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Supplementary information S1 (box)
Top 1,000 genes analysis (PDF 745 kb)
Supplementary information S2 (figure)
Genes viewed in the Allen Brain Atlas. (PDF 172 kb)
Related links
Related links
FURTHER INFORMATION
Allen Developing Mouse Brain Atlas
Allen Institute for Brain Science
Allen Institute Human Cortex Study
Allen Institute Mouse Diversity Study
Allen Institute Transgenic Mouse Study
Allen Mouse Brain Atlas (original ABA)
Brain Explorer self-guided tutorial for education
International Neuroinformatics Coordinating Facility
Mutant Mouse Regional Resource Centers (MMRRC)
Rights and permissions
About this article
Cite this article
Jones, A., Overly, C. & Sunkin, S. The Allen Brain Atlas: 5 years and beyond. Nat Rev Neurosci 10, 821–828 (2009). https://doi.org/10.1038/nrn2722
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrn2722
This article is cited by
-
Anxiety and dysautonomia symptoms in patients with a NaV1.7 mutation and the potential benefits of low-dose short-acting guanfacine
Clinical Autonomic Research (2023)
-
EBRAINS Live Papers - Interactive Resource Sheets for Computational Studies in Neuroscience
Neuroinformatics (2023)
-
Connecting DCX, COMT and FMR1 in social behavior and cognitive impairment
Behavioral and Brain Functions (2022)
-
Neurocognitive patterns across genetic levels in behavioral variant frontotemporal dementia: a multiple single cases study
BMC Neurology (2022)
-
AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus
Acta Neuropathologica Communications (2022)