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An anatomic gene expression atlas of the adult mouse brain

Abstract

Studying gene expression provides a powerful means of understanding structure-function relationships in the nervous system. The availability of genome-scale in situ hybridization datasets enables new possibilities for understanding brain organization based on gene expression patterns. The Anatomic Gene Expression Atlas (AGEA) is a new relational atlas revealing the genetic architecture of the adult C57Bl/6J mouse brain based on spatial correlations across expression data for thousands of genes in the Allen Brain Atlas (ABA). The AGEA includes three discovery tools for examining neuroanatomical relationships and boundaries: (1) three-dimensional expression-based correlation maps, (2) a hierarchical transcriptome-based parcellation of the brain and (3) a facility to retrieve from the ABA specific genes showing enriched expression in local correlated domains. The utility of this atlas is illustrated by analysis of genetic organization in the thalamus, striatum and cerebral cortex. The AGEA is a publicly accessible online computational tool integrated with the ABA (http://mouse.brain-map.org/agea).

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Figure 1: Construction and representation of the Anatomic Gene Expression Atlas (AGEA).
Figure 2: The ventral posterior complex (VP) of the thalamus.
Figure 3: The parafascicular nucleus of the thalamus.
Figure 4: Genetic organization of the striatum.
Figure 5: Anatomic gene markers for the dorsal-ventral striatum.
Figure 6: AGEA and cortical topography.

References

  1. MacKenzie-Graham, A. et al. The informatics of a C57BL/6J mouse brain atlas. Neuroinformatics 1, 397–410 (2003).

    Article  Google Scholar 

  2. Toga, A.W. & Thompson, P.M. in Brain Mapping: The Systems (eds. Toga, A.W. & Mazziotta, J.C.): 4–5 (Academic Press, San Diego, 2000).

    Google Scholar 

  3. Swanson, L.W. Structure of the Rat Brain (Academic Press, San Diego, 2004).

    Google Scholar 

  4. Paxinos, G. & Franklin, K.B.J. The Mouse Brain in Stereotaxic Coordinates (Academic Press, San Diego, 2004).

  5. Dong, H.W. The Allen Reference Atlas: A Digital Color Brain Atlas of the C57BL/6J Male Mouse (John Wiley & Sons, Hoboken, New Jersey, USA, 2008).

    Google Scholar 

  6. Ma, Y. et al. A three-dimensional digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy. Neuroscience 135, 1203–1215 (2005).

    CAS  Article  Google Scholar 

  7. Toga, A.W., Thompson, P.M., Mori, S., Amunts, K. & Zilles, K. Towards multimodal atlases of the human brain. Nat. Rev. Neurosci. 7, 952–966 (2006).

    CAS  Article  Google Scholar 

  8. MacKenzie-Graham, A. et al. A multimodal, multidimensional atlas of the C57BL/6J mouse brain. J. Anat. 204, 93–102 (2004).

    Article  Google Scholar 

  9. Van Essen, D.C., Drury, H.A., Joshi, S. & Miller, M.I. Functional and structural mapping of human cerebral cortex: solutions are in the surfaces. Proc. Natl. Acad. Sci. USA 95, 788–795 (1998).

    CAS  Article  Google Scholar 

  10. Gee, C.E. & Roberts, J.L. In situ hybridization histochemistry: a technique for the study of gene expression in single cells. DNA 2, 157–163 (1983).

    CAS  Article  Google Scholar 

  11. Visel, A., Thaller, C. & Eichele, G. GenePaint.org: an atlas of gene expression patterns in the mouse embryo. Nucleic Acids Res. 32, D552–D556 (2004).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  13. Sunkin, S.M. & Hohmann, J. G. Insights from spatially mapped gene expression in the mouse brain. Hum. Mol. Genet. 16 (Spec. No. 2): R209–R219 (2007).

    CAS  Article  Google Scholar 

  14. Bonner, R.F. et al. Laser capture microdissection: molecular analysis of tissue. Science 278, 1481–1483 (1997).

    CAS  Article  Google Scholar 

  15. Zapala, M.A. et al. Adult mouse brain gene expression patterns bear an embryologic imprint. Proc. Natl. Acad. Sci. USA 102, 10357–10362 (2005).

    CAS  Article  Google Scholar 

  16. Flames, N. et al. Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J. Neurosci. 27, 9682–9695 (2007).

    CAS  Article  Google Scholar 

  17. Ng, L.L. et al. Neuroinformatics for genome-wide 3D gene expression mapping in the mouse brain. IEEE Trans. Comput. Biol. Bioinformatics 4, 382–393 (2007).

    CAS  Article  Google Scholar 

  18. Price, J.L. in The Rat Nervous System (ed. Paxinos, G.) 632–633 (Academic Press, Sydney, 1995).

    Google Scholar 

  19. Sherman, S.M. & Guillery, R.W. Exploring the Thalamus and its Role in Cortical Function (MIT Press, Cambridge, Massachusetts, USA, 2006).

    Google Scholar 

  20. Nakamura, Y., Otake, K. & Tokuno, H. The parafascicular nucleus relays spinal inputs to the striatum: an electron microscope study in the rat. Neurosci. Res. 56, 73–79 (2006).

    Article  Google Scholar 

  21. Marini, G., Pianca, L. & Tredici, G. Thalamocortical projection from the parafascicular nucleus to layer V pyramidal cells in frontal and cingulate areas of the rat. Neurosci. Lett. 203, 81–84 (1996).

    CAS  Article  Google Scholar 

  22. Voorn, P., Vanderschuren, L.J., Groenewegen, H.J., Robbins, T.W. & Pennartz, C.M. Putting a spin on the dorsal-ventral divide of the striatum. Trends Neurosci. 27, 468–474 (2004).

    CAS  Article  Google Scholar 

  23. Brodmann, K. in Some Papers on the Cerebral Cortex [originally published 1909; translated as On the comparative localization of the cortex] 201–230 (Thomas, Springfield, Illinois, USA, 1960).

    Google Scholar 

  24. Yamamori, T. & Rockland, K.S. Neocortical areas, layers, connections, and gene expression. Neurosci. Res. 55, 11–27 (2006).

    CAS  Article  Google Scholar 

  25. Mountcastle, V.B. Perceptual Neuroscience: The Cerebral Cortex (Harvard University Press, Cambridge, Massachusetts, USA, 1998).

    Google Scholar 

  26. Kruskal, J.B. Non-metric multidimensional scaling: a numerical method. Psychometrika 29, 115–129 (1964).

    Article  Google Scholar 

  27. Paxinos, G. The Rat Nervous System (Academic Press, New York, 1995).

    Google Scholar 

  28. Alvarez-Buylla, A. & Garcia-Verdugo, J.M. Neurogenesis in adult subventricular zone. J. Neurosci. 22, 629–634 (2002).

    CAS  Article  Google Scholar 

  29. Abrous, D.N., Koehl, M. & Le Moal, M. Adult neurogenesis: from precursors to network and physiology. Physiol. Rev. 85, 523–569 (2005).

    CAS  Article  Google Scholar 

  30. Yushkevich, P.A. et al. Using MRI to build a 3D reference atlas of the mouse brain from histological images. Proc. Intl. Soc. Magn. Reson. Med. Annu. Mtg. 13, 2809 (2005).

    Google Scholar 

  31. Kruskal, J.B. Multidimensional scaling by optimizing goodness of fit to a nonmetric hypothesis. Psychometrika 29, 1–27 (1964).

    Article  Google Scholar 

  32. DeGroot, M.H. & Schervish, M.J. Probability and Statistics (Addison-Wesley, Boston, 2002).

    Google Scholar 

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Acknowledgements

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. The authors also thank D. Haynor of the University of Washington, Department of Neuroradiology, and C. Thompson of the Allen Institute.

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Authors and Affiliations

Authors

Contributions

L.N., CL. and C.D. built the AGEA application; LN., A.B, J.W.B., H.B., P.P.M. and M.H. performed the analyses; H.-W.D., L.P. and J.H. interpreted neuroanatomy; L.K. and S.P. provided informatics support; E.S.L., D.J.A., A.J.R., M.H. provided overall guidance; and L.N., C.C.O., A.B., S.M.S. and M.H. wrote the manuscript.

Corresponding author

Correspondence to Michael Hawrylycz.

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Supplementary Methods (including Supplementary Figures 1–4) and Supplementary Results (including Supplementary Figures 5–10 and Supplementary Tables 1–7) (PDF 5131 kb)

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Ng, L., Bernard, A., Lau, C. et al. An anatomic gene expression atlas of the adult mouse brain. Nat Neurosci 12, 356–362 (2009). https://doi.org/10.1038/nn.2281

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