Skip to main content

High-resolution gene expression atlases for adult and developing mouse brain and spinal cord

Abstract

Knowledge of the structure, genetics, circuits, and physiological properties of the mammalian brain in both normal and pathological states is ever increasing as research labs worldwide probe the various aspects of brain function. Until recently, however, comprehensive cataloging of gene expression across the central nervous system has been lacking. The Allen Institute for Brain Science, as part of its mission to propel neuroscience research, has completed several large gene-mapping projects in mouse, nonhuman primate, and human brain, producing informative online public resources and tools. Here we present the Allen Mouse Brain Atlas, covering ~20,000 genes throughout the adult mouse brain; the Allen Developing Mouse Brain Atlas, detailing expression of approximately 2,000 important developmental genes across seven embryonic and postnatal stages of brain growth; and the Allen Spinal Cord Atlas, revealing expression for ~20,000 genes in the adult and neonatal mouse spinal cords. Integrated data-mining tools, including reference atlases, informatics analyses, and 3-D viewers, are described. For these massive-scale projects, high-throughput industrial techniques were developed to standardize and reliably repeat experimental goals. To verify consistency and accuracy, a detailed analysis of the 1,000 most viewed genes for the adult mouse brain (according to website page views) was performed by comparing our data with peer-reviewed literature and other databases. We show that our data are highly consistent with independent sources and provide a comprehensive compendium of information and tools used by thousands of researchers each month. All data and tools are freely available via the Allen Brain Atlas portal (www.brain-map.org).

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  • Allen institute for brain science (2010) Comparison of the top 1000 genes (October 2010), Allen mouse brain atlas. Available at http://help.brain-map.org/display/mousebrain/Documentation. Last accessed March 2012

  • Belgard TG, Marques AC, Oliver PL, Abaan HO, Sirey TM et al (2011) A transcriptomic atlas of mouse neocortical layers. Neuron 71:605–616

    PubMed  Article  CAS  Google Scholar 

  • Bernard A, Lubbers LS, Tanis KQ, Luo R, Podtelezhnikov AA et al (2012) Transcriptional architecture of the primate neocortex. Neuron 73:1083–1099

    PubMed  Article  CAS  Google Scholar 

  • Castel M, Morris JF (1988) The neurophysin-containing innervation of the forebrain of the mouse. Neuroscience 24:937–966

    PubMed  Article  CAS  Google Scholar 

  • Chen JF, Qin ZH, Szele F, Bai G, Weiss B (1991) Neuronal localization and modulation of the D2 dopamine receptor mRNA in brain of normal mice and mice lesioned with 6-hydroxydopamine. Neuropharmacology 30:927–941

    PubMed  Article  CAS  Google Scholar 

  • Chen Y, Brunson KL, Muller MB, Cariaga W, Baram TZ (2000) Immunocytochemical distribution of corticotropin-releasing hormone receptor type-1 (CRF(1))-like immunoreactivity in the mouse brain: light microscopy analysis using an antibody directed against the C-terminus. J Comp Neurol 420:305–323

    PubMed  Article  CAS  Google Scholar 

  • Cheung CC, Hohmann JG, Clifton DK, Steiner RA (2001) Distribution of galanin messenger RNA-expressing cells in murine brain and their regulation by leptin in regions of the hypothalamus. Neuroscience 103:423–432

    PubMed  Article  CAS  Google Scholar 

  • Clark MS, McDevitt RA, Neumaier JF (2006) Quantitative mapping of tryptophan hydroxylase-2,5-HT1A, 5-HT1B, and serotonin transporter expression across the anteroposterior axis of the rat dorsal and median raphe nuclei. J Comp Neurol 498:611–623

    PubMed  Article  CAS  Google Scholar 

  • Danik M, Cassoly E, Manseau F, Sotty F, Mouginot D et al (2005) Frequent coexpression of the vesicular glutamate transporter 1 and 2 genes, as well as coexpression with genes for choline acetyltransferase or glutamic acid decarboxylase in neurons of rat brain. J Neurosci Res 81:506–521

    PubMed  Article  CAS  Google Scholar 

  • de Foubert G, O’Neill MJ, Zetterstrom TS (2007) Acute onset by 5-HT(6)-receptor activation on rat brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA expression. Neuroscience 147:778–785

    PubMed  Article  Google Scholar 

  • Dong HW (2008) The Allen reference atlas: a digital color brain atlas of the C57BL/6J male mouse. Wiley, Hoboken

    Google Scholar 

  • Ferland RJ, Cherry TJ, Preware PO, Morrisey EE, Walsh CA (2003) Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain. J Comp Neurol 460:266–279

    PubMed  Article  CAS  Google Scholar 

  • Ferraguti F, Zoli M, Aronsson M, Agnati LF, Goldstein M et al (1990) Distribution of glutamic acid decarboxylase messenger RNA-containing nerve cell populations of the male rat brain. J Chem Neuroanat 3:377–396

    PubMed  CAS  Google Scholar 

  • Frantz GD, Tobin AJ (1994) Cellular distribution of calbindin D28 K mRNAs in the adult mouse brain. J Neurosci Res 37:287–302

    PubMed  Article  CAS  Google Scholar 

  • French L, Pavlidis P (2011) Relationships between gene expression and brain wiring in the adult rodent brain. PLoS Comput Biol 7:e1001049

    PubMed  Article  CAS  Google Scholar 

  • Garcia MM, Cusick CG, Harlan RE (1993) Protein kinase C-delta in rat brain: association with sensory neuronal hierarchies. J Comp Neurol 331:375–388

    PubMed  Article  CAS  Google Scholar 

  • Gee CE, Chen CL, Roberts JL, Thompson R, Watson SJ (1983) Identification of proopiomelanocortin neurones in rat hypothalamus by in situ cDNA-mRNA hybridization. Nature 306:374–376

    PubMed  Article  CAS  Google Scholar 

  • Gehlert DR, Chronwall BM, Schafer MP, O’Donohue TL (1987) Localization of neuropeptide Y messenger ribonucleic acid in rat and mouse brain by in situ hybridization. Synapse 1:25–31

    PubMed  Article  CAS  Google Scholar 

  • Gong S, Zheng C, Doughty ML, Losos K, Didkovsky N et al (2003) A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 425:917–925

    PubMed  Article  CAS  Google Scholar 

  • Gotti S, Sica M, Viglietti-Panzica C, Panzica G (2005) Distribution of nitric oxide synthase immunoreactivity in the mouse brain. Microsc Res Tech 68:13–35

    PubMed  Article  CAS  Google Scholar 

  • Herzog E, Gilchrist J, Gras C, Muzerelle A, Ravassard P et al (2004) Localization of VGLUT3, the vesicular glutamate transporter type 3, in the rat brain. Neuroscience 123:983–1002

    PubMed  Article  CAS  Google Scholar 

  • Hisano S, Hoshi K, Ikeda Y, Maruyama D, Kanemoto M et al (2000) Regional expression of a gene encoding a neuron-specific Na(+)-dependent inorganic phosphate cotransporter (DNPI) in the rat forebrain. Brain Res Mol Brain Res 83:34–43

    PubMed  Article  CAS  Google Scholar 

  • Hofer M, Pagliusi SR, Hohn A, Leibrock J, Barde YA (1990) Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain. EMBO J 9:2459–2464

    PubMed  CAS  Google Scholar 

  • Huang XF, Koutcherov I, Lin S, Wang HQ, Storlien L (1996) Localization of leptin receptor mRNA expression in mouse brain. Neuroreport 7:2635–2638

    PubMed  Article  CAS  Google Scholar 

  • Jennes L, Stumpf WE, Kalivas PW (1982) Neurotensin: topographical distribution in rat brain by immunohistochemistry. J Comp Neurol 210:211–224

    PubMed  Article  CAS  Google Scholar 

  • Jensen CH, Meyer M, Schroder HD, Kliem A, Zimmer J et al (2001) Neurons in the monoaminergic nuclei of the rat and human central nervous system express FA1/dlk. Neuroreport 12:3959–3963

    PubMed  Article  CAS  Google Scholar 

  • Jones AR, Overly CC, Sunkin SM (2009) The Allen brain atlas: 5 years and beyond. Nat Rev Neurosci 10:821–828

    PubMed  Article  CAS  Google Scholar 

  • Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X et al (2011) Spatio-temporal transcriptome of the human brain. Nature 478:483–489

    PubMed  Article  CAS  Google Scholar 

  • Klein R, Martin-Zanca D, Barbacid M, Parada LF (1990) Expression of the tyrosine kinase receptor gene trkB is confined to the murine embryonic and adult nervous system. Development 109:845–850

    PubMed  CAS  Google Scholar 

  • Korpi ER, Kleingoor C, Kettenmann H, Seeburg PH (1993) Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor. Nature 361:356–359

    PubMed  Article  CAS  Google Scholar 

  • Koylu EO, Couceyro PR, Lambert PD, Kuhar MJ (1998) Cocaine- and amphetamine-regulated transcript peptide immunohistochemical localization in the rat brain. J Comp Neurol 391:115–132

    PubMed  Article  CAS  Google Scholar 

  • Kurrasch DM, Cheung CC, Lee FY, Tran PV, Hata K et al (2007) The neonatal ventromedial hypothalamus transcriptome reveals novel markers with spatially distinct patterning. J Neurosci 27:13624–13634

    PubMed  Article  CAS  Google Scholar 

  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    PubMed  Article  CAS  Google Scholar 

  • Lau C, Ng L, Thompson C, Pathak S, Kuan L et al (2008) Exploration and visualization of gene expression with neuroanatomy in the adult mouse brain. BMC Bioinformatics 9:153

    PubMed  Article  Google Scholar 

  • Lauterborn JC, Isackson PJ, Montalvo R, Gall CM (1993) In situ hybridization localization of choline acetyltransferase mRNA in adult rat brain and spinal cord. Brain Res Mol Brain Res 17:59–69

    PubMed  Article  CAS  Google Scholar 

  • Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A et al (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445:168–176

    PubMed  Article  CAS  Google Scholar 

  • Lin S, Boey D, Lee N, Schwarzer C, Sainsbury A et al (2006) Distribution of prodynorphin mRNA and its interaction with the NPY system in the mouse brain. Neuropeptides 40:115–123

    PubMed  Article  CAS  Google Scholar 

  • Lindblad-Toh K, Garber M, Zuk O, Lin MF, Parker BJ et al (2011) A high-resolution map of human evolutionary constraint using 29 mammals. Nature 478:476–482

    PubMed  Article  CAS  Google Scholar 

  • Liodis P, Denaxa M, Grigoriou M, Akufo-Addo C, Yanagawa Y et al (2007) Lhx6 activity is required for the normal migration and specification of cortical interneuron subtypes. J Neurosci 27:3078–3089

    PubMed  Article  CAS  Google Scholar 

  • Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA et al (2010) A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 13:133–140

    PubMed  Article  CAS  Google Scholar 

  • Magdaleno S, Jensen P, Brumwell CL, Seal A, Lehman K et al (2006) BGEM: an in situ hybridization database of gene expression in the embryonic and adult mouse nervous system. PLoS Biol 4:e86

    PubMed  Article  Google Scholar 

  • Mansour A, Meador-Woodruff JH, Zhou Q, Civelli O, Akil H et al (1992) A comparison of D1 receptor binding and mRNA in rat brain using receptor autoradiographic and in situ hybridization techniques. Neuroscience 46:959–971

    PubMed  Article  CAS  Google Scholar 

  • Martin PM, O’Callaghan JP (1995) A direct comparison of GFAP immunocytochemistry and GFAP concentration in various regions of ethanol-fixed Rat and mouse brain. J Neurosci Methods 58:181–192

    PubMed  Article  CAS  Google Scholar 

  • Martin LJ, Blackstone CD, Levey AI, Huganir RL, Price DL (1993) AMPA glutamate receptor subunits are differentially distributed in rat brain. Neuroscience 53:327–358

    PubMed  Article  CAS  Google Scholar 

  • Merchenthaler I, Csernus V, Csontos C, Petrusz P, Mess B (1988) New data on the immunocytochemical localization of thyrotropin-releasing hormone in the rat central nervous system. Am J Anat 181:359–376

    PubMed  Article  CAS  Google Scholar 

  • Moldrich G, Wenger T (2000) Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study. Peptides 21:1735–1742

    PubMed  Article  CAS  Google Scholar 

  • Ng L, Bernard A, Lau C, Overly CC, Dong HW et al (2009) An anatomic gene expression atlas of the adult mouse brain. Nat Neurosci 12:356–362

    PubMed  Article  CAS  Google Scholar 

  • Ochiishi T, Terashima T, Yamauchi T (1994) Specific distribution of Ca2+/calmodulin-dependent protein kinase II alpha and beta isoforms in some structures of the rat forebrain. Brain Res 659:179–193

    PubMed  Article  CAS  Google Scholar 

  • Petit A, Sanders AD, Kennedy TE, Tetzlaff W, Glattfelder KJ et al (2011) Adult spinal cord radial glia display a unique progenitor phenotype. PloS One 6:e24538

    PubMed  Article  CAS  Google Scholar 

  • Resibois A, Rogers JH (1992) Calretinin in rat brain: an immunohistochemical study. Neuroscience 46:101–134

    PubMed  Article  CAS  Google Scholar 

  • Romano C, Sesma MA, McDonald CT, O’Malley K, Van den Pol AN et al (1995) Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain. J Comp Neurol 355:455–469

    PubMed  Article  CAS  Google Scholar 

  • Rubenstein JL, Martinez S, Shimamura K, Puelles L (1994) The embryonic vertebrate forebrain: the prosomeric model. Science 266:578–580

    PubMed  Article  CAS  Google Scholar 

  • Sengul G, Puchalski RB, Watson C (2012) Cytoarchitecture of the spinal cord of the postnatal (P4) mouse. Anat Rec (Hoboken) 295(5):837–845

    Article  Google Scholar 

  • Seto-Ohshima A, Emson PC, Berchtold MW, Heizmann CW (1989) Localization of parvalbumin mRNA in rat brain by in situ hybridization histochemistry. Exp Brain Res 75:653–658

    PubMed  Article  CAS  Google Scholar 

  • Shigemoto R, Nakanishi S, Mizuno N (1992) Distribution of the mRNA for a metabotropic glutamate receptor (mGluR1) in the central nervous system: an in situ hybridization study in adult and developing rat. J Comp Neurol 322:121–135

    PubMed  Article  CAS  Google Scholar 

  • Shimada S, Kitayama S, Walther D, Uhl G (1992) Dopamine transporter mRNA: dense expression in ventral midbrain neurons. Brain Res Mol Brain Res 13:359–362

    PubMed  Article  CAS  Google Scholar 

  • Shimogori T, Lee DA, Miranda-Angulo A, Yang Y, Wang H et al (2010) A genomic atlas of mouse hypothalamic development. Nat Neurosci 13:767–775

    PubMed  Article  CAS  Google Scholar 

  • Stoykova A, Gruss P (1994) Roles of Pax-genes in developing and adult brain as suggested by expression patterns. J Neurosci 14:1395–1412

    PubMed  CAS  Google Scholar 

  • Takeda K, Inoue H, Tanizawa Y, Matsuzaki Y, Oba J et al (2001) WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain. Hum Mol Genet 10:477–484

    PubMed  Article  CAS  Google Scholar 

  • Van Essen DC, Ugurbil K, Auerbach E, Barch D, Behrens TE et al (2012) The human connectome project: a data acquisition perspective. NeuroImage. doi:10.1016/j.neuroimage.2012.02.018

  • Van Pett K, Viau V, Bittencourt JC, Chan RK, Li HY et al (2000) Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse. J Comp Neurol 428:191–212

    PubMed  Article  Google Scholar 

  • Warden MK, Young WS (1988) Distribution of cells containing mRNAs encoding substance P and neurokinin B in the rat central nervous system. J Comp Neurol 272:90–113

    PubMed  Article  CAS  Google Scholar 

  • Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF et al (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–562

    PubMed  Article  CAS  Google Scholar 

  • Watson C, Paxinos G, Kayalioglu G (2008) The spinal cord, 1st edn. Academic Press, Waltham

    Google Scholar 

  • Wei LC, Shi M, Chen LW, Cao R, Zhang P et al (2002) Nestin-containing cells express glial fibrillary acidic protein in the proliferative regions of central nervous system of postnatal developing and adult mice. Brain Res Dev Brain Res 139:9–17

    PubMed  Article  CAS  Google Scholar 

  • Wei Q, Lu XY, Liu L, Schafer G, Shieh KR et al (2004) Glucocorticoid receptor overexpression in forebrain: a mouse model of increased emotional lability. Proc Natl Acad Sci USA 101:11851–11856

    PubMed  Article  CAS  Google Scholar 

  • Wright DE, Seroogy KB, Lundgren KH, Davis BM, Jennes L (1995) Comparative localization of serotonin1A, 1C, and 2 receptor subtype mRNAs in rat brain. J Comp Neurol 351:357–373

    PubMed  Article  CAS  Google Scholar 

  • Yamada K, Sakai M, Okamura H, Ibata Y, Nagatsu I (1992) Detection of tyrosine hydroxylase and phenylethanolamine-N-methyltransferase messenger RNAs in the mouse adrenal gland and the brain by in situ hybridization. Histochemistry 97:201–206

    PubMed  Article  CAS  Google Scholar 

  • Yang HK, Sundholm-Peters NL, Goings GE, Walker AS, Hyland K et al (2004) Distribution of doublecortin expressing cells near the lateral ventricles in the adult mouse brain. J Neurosci Res 76:282–295

    PubMed  Article  CAS  Google Scholar 

  • Yoneshima H, Yamasaki S, Voelker CC, Molnar Z, Christophe E et al (2006) Er81 is expressed in a subpopulation of layer 5 neurons in rodent and primate neocortices. Neuroscience 137:401–412

    PubMed  Article  CAS  Google Scholar 

  • Zagon IS, Isayama T, McLaughlin PJ (1994) Preproenkephalin mRNA expression in the developing and adult rat brain. Brain Res Mol Brain Res 21:85–98

    PubMed  Article  CAS  Google Scholar 

  • Zavitsanou K, Triarhou LC, Kouvelas ED, Mitsacos A, Palacios JM et al (2002) Somatostatin, cholecystokinin and neuropeptide Y mRNAs in normal and weaver mouse brain. J Neural Transm 109:1337–1351

    PubMed  Article  CAS  Google Scholar 

  • Zeng H, Shen EH, Hohmann JG, Oh SW, Bernard A et al (2012) Large-scale cellular-resolution gene profiling in human neocortex reveals species-specific molecular signatures. Cell 149(2):483–496

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the Allen Institute founders, Paul G. Allen and Jody Allen, for their vision, encouragement, and support. The Allen Spinal Cord Atlas was made possible by a unique funding consortium comprising public and private entities, including The ALS Association, PVA Research Foundation (grant No. 2525), Wyeth Research, National Multiple Sclerosis Society, International Spinal Research Trust, PEMCO Insurance, and philanthropist and Allen Institute founder Paul G. Allen, as well as other anonymous donors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alex M. Henry.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Henry, A.M., Hohmann, J.G. High-resolution gene expression atlases for adult and developing mouse brain and spinal cord. Mamm Genome 23, 539–549 (2012). https://doi.org/10.1007/s00335-012-9406-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00335-012-9406-2

Keywords

  • Mouse Brain
  • Adult Mouse Brain
  • Spinal Cord Disease
  • Allen Institute
  • Gene Expression Atlas