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The Genetic Geography of the Brain

The patterning of gene usage across the structures of the adult human brain is highly stereotyped and reproducible. This dynamic heatmap represents the common structure of this patterning across individuals, specifically the number of genes that are differentially expressed between pairs of anatomic regions in at least 5 of the 6 brains measured. Hotter red shades represent brain regions that are very different in their transcriptional regulation, while cooler blue shades represent regions of high similarity.

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Structures Emerge

Cerebral Cortex

Biologically interesting features related to anatomical structure emerges from this map. Our enormous cerebral cortex appears quite homogeneous, consistent with the idea that the basic architecture across the entire cortex is similar or “canonical.” This is indicated by the blue shading representing high similarity in the large upper left region of the map comprising cortical gyri ordered from the frontal pole (fro) to cingulate gyrus (CgGP-s).

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Structures Emerge

Visual Cortex

The main exception to this cortical homogeneity is the primary visual cortex. This highly specialized cortical region is anatomically, functionally and transcriptionally distinct from other cortical regions, as apparent by the notable band made by samples from the striate portion of the lingual gyrus ("LIG") that contains this region.

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Structures Emerge

Hippocampus

The hippocampus is extensively studied for its critical role in learning and memory, and shows a distinct pattern of gene expression across its highly distinct and stereotyped anatomical divisions including the dentate gyrus (DG), pyramidal cell layers (CA1, CA2, CA3 and CA4), and subiculum (S). This patterning is different from its close relative the cortex, and even more distinct from that of evolutionarily older brain regions

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Structures Emerge

Cerebellum

What particularly distinguishes a number of major brain regions is internal homogeneity across subdivisions. This is most apparent for the cerebellum, with samples from different cerebellar lobes listed from “PV-IV” through “He-VIIB” showing no internally differentially expressing genes that are reproducible across individuals.

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Structures Emerge

Amygdala

Similarly, the individual nuclei that make up the amygdala, a structure involved in emotional behaviors, are very similar to one another while very different from other brain regions.

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Structures Emerge

Thalamus

The thalamus, which receives sensory information from the periphery and sends it to the cortex, also shows a great deal of internal complexity among constituent nuclei. These nuclei carry information from different senses such as vision, touch and hearing, and have reciprocal input with the neocortex.

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Structures Emerge

Brainstem Nuclei

Interestingly, the brainstem nuclei (“Cu” through “8ve”) are all highly transcriptionally distinct from one another. Presumably this reflects the highly distinctive functional roles played by these different structures and specialized sets of genes necessary for these functions.

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Structures Emerge

Overall, this gene expression patterning mirrors the gross anatomical partitioning apparent from classical anatomical, developmental and functional studies of the human brain, while providing the genes that underlie these functional partitions. Furthermore, these gene expression patterns reveal features about the cellular makeup of different brain regions. For example, among the most distinctive regions are those that are comprised primarily of non-neuronal cells, including the corpus callosum (cc) and choroid plexus (CPLV).

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Diving Down

This dynamic map allows for direct access to the genes showing reproducible differential expression between structure pairs by clicking on a fixed square. For example, clicking on the square representing the pair “SFG-m” (Superior frontal gyrus – medial aspect in the frontal lobe) and “LiG-str” (Lingual gyrus – striate containing primary visual cortex in the occipital lobe) returns a list of genes highly differentially expressed between these cortical regions. Included in this list is the proto-oncogene receptor tyrosine kinase MET. MET is widely known to have a strong anterior (frontal) to posterior (occipital) differential relationship as demonstrated here by clicking on the gene symbol to view the microarray heatmap for this gene.

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