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Comparative Study
. 2005 Jul 19;102(29):10357-62.
doi: 10.1073/pnas.0503357102. Epub 2005 Jul 7.

Adult mouse brain gene expression patterns bear an embryologic imprint

Affiliations
Comparative Study

Adult mouse brain gene expression patterns bear an embryologic imprint

Matthew A Zapala et al. Proc Natl Acad Sci U S A. .

Abstract

The current model to explain the organization of the mammalian nervous system is based on studies of anatomy, embryology, and evolution. To further investigate the molecular organization of the adult mammalian brain, we have built a gene expression-based brain map. We measured gene expression patterns for 24 neural tissues covering the mouse central nervous system and found, surprisingly, that the adult brain bears a transcriptional "imprint" consistent with both embryological origins and classic evolutionary relationships. Embryonic cellular position along the anterior-posterior axis of the neural tube was shown to be closely associated with, and possibly a determinant of, the gene expression patterns in adult structures. We also observed a significant number of embryonic patterning and homeobox genes with region-specific expression in the adult nervous system. The relationships between global expression patterns for different anatomical regions and the nature of the observed region-specific genes suggest that the adult brain retains a degree of overall gene expression established during embryogenesis that is important for regional specificity and the functional relationships between regions in the adult. The complete collection of extensively annotated gene expression data along with data mining and visualization tools have been made available on a publicly accessible web site (www.barlow-lockhart-brainmapnimhgrant.org).

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Figures

Fig. 1.
Fig. 1.
The adult brain bears a gene expression imprint based on embryologic origin and classic evolutionary complexity. (A) Pearson correlation heat map matrix of all brain samples. The white boxes outline the classic evolutionarily related regions of the archicortex (A) (HiF, CA1, CA3, and DG), paleocortex (P) (Amg, EntCx, and PrhCx), and neocortex (N) (Cx and MtrCx). Samples with very similar gene expression profiles corresponding to a higher correlation coefficient are denoted by dark red, and map positions corresponding to brain regions with dissimilar gene expression profiles appear dark blue. (B) Unsupervised hierarchical cluster dendrogram. (Left) The dendrogram relating structures to one another. (Right) A schematic of the developing mouse brain with the five vesicle regions color-coded. The color chart shows the derivatives of these embryonic brain vesicles in the context of the dendrogram. The hatched boxes indicate brain structures formed by inductive events. A, archicortex; P, paleocortex; N, neocortex.
Fig. 2.
Fig. 2.
Genes with region-specific expression patterns function in development, pattern specification, and morphogenesis. (A) The abscissa indicates the functional categories from the gotm program. Within the GO biological process category, only “development” and “regulation of biological process” showed significant overrepresentation (*, P < 0.01). The ordinate indicates the number of genes observed in each category compared with the number of genes expected by chance. The significantly overrepresented categories are noted by an asterisk. (B) The GO subcategories in “development” from A that are significantly overrepresented in the set of genes with region-specific expression patterns. The GO categories are noted along the abscissa; the negative logarithm (base 10) of the P value is given along the ordinate. Functional categories significantly overrepresented are noted by an asterisk. (C) Reference brain atlas displayed in the three orthogonal planes. This Nissl-stained C57BL/6N mouse brain atlas comprises 462 coronal sections at 30-μm thickness, digitized at a resolution of 1.3 μm/pixel. The sagittal and horizontal planes are “virtual” sections dynamically constructed from the coronal sections. (D) 3D atlas of brain regions. Specific brain regions along the rostrocaudal neuraxis are color-coded. (E) The expression levels of the homeobox and other embryonic patterning genes expressed in the adult mouse brain are shown for each region. A complete list of these embryonic patterning genes is available upon request.

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