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Basal gangliaSummaryBasal ganglia originate from the telencephalon (forebrain) and is a collective name for subcortical nuclei, striatum and pallidum. This structure is developmentally related to the cerebral cortex, the amygdala, the olfactory, and the hippocampal formation. An important role of the basal ganglia is in the control of movement while they are also pivotal in addiction and reward mechanisms. The transcriptome analysis shows that 73% (n=14685) of all human protein-coding genes (n=20090) are expressed in the human basal ganglia. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 12629 of all mouse one-to-one orthologues (n=16320) are expressed in the mouse basal ganglia and that 13274 of all pig orthologues (n=15829) are expressed in the pig basal ganglia. Gene classification based on regional RNA expression in human, pig and mouse basal ganglia defines 79 genes as basal ganglia enriched in either of the three species, and 31 out of those genes show highest expression levels in basal ganglia in all three species.
Figure 1. Schematic drawing of the human brain, indicating the location of basal ganglia from a sagittal view. Anatomical divisionsBasal ganglia include a collection of subcortical nuclei, striatum, and pallidum. These are subdivisions of the regions included in the collective name of basal ganglia. The caudate nucleus and putamen are often referred to as the striatum and are together with globus pallidus a central relay between the brainstem and cerebral cortex for signals of voluntary movements while the nucleus accumbens plays an important role in addiction and reward systems. The unique look of the striatum is caused by bundles of white matter (myelinated axons densely packed in tracts) surrounded by gray matter, with more neuronal cell bodies. The type of neurons in the gray matter depend on the sub-region of the basal ganglia. The visual effect of white vs gray matter in caudate putamen of the mouse brain is shown by TH in gray matter and CNP in white matter showing the complementary staining pattern. Regionally elevated protein expression in human
Figure 2. Schematic drawing of the human brain, indicating the location of basal ganglia from a coronal perspective. The transcriptome analysis shows that 73% (n=14685) of all human proteins (n=20090) are expressed in basal ganglia. 199 genes show an elevated expression level in basal ganglia compared to other regions of the brain. The human basal ganglia subregions include caudate nucleus, putamen, globus pallidus and nucleus accumbens among others. The highest mean value of the individual sub-regions was used as representation of basal ganglia as one of the 13 brain regions.
Table 1: Number of genes within the different categories of regionally elevated expression, in human basal ganglia
Elevated expression in basal ganglia compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in basal ganglia compared to all other regions), group enriched (at least four-fold higher mRNA levels in a group of 2-5 regions) and regionally enhanced (at least four-fold higher mRNA levels in basal ganglia compared to the average of all regions), The number of genes in the individual category is shown in Table 1. In Table 2, the 12 genes with the highest level of regional specificity among the 14 enriched genes are listed. Table 2. The 14 genes with the highest level of enriched expression in human basal ganglia. "Predicted localization" shows the classification of each gene into three main classes: Secreted, Membrane, and Intracellular, where the latter consists of genes without any predicted membrane and secreted features. RS-score (Regional Specificity score) corresponds to the score calculated as the fold change to the second highest tissue.
Proteins specifically detected in human caudate nucleusThe tissue atlas includes TMA cores from caudate nucleus in standard profiling procedures, enabling high throughput analysis of the protein location in caudate nucleus, here are a few examples of proteins specifically located in human caudate nucleus. Regionally elevated protein expression in mouseThe mouse basal ganglia is similar to the human basal ganglia divided into striatum and pallidum, a collection of subcortical nuclei involved in movement control and processing. The subregions of the mouse brain included in this analysis are caudate putamen, septum and ventral forebrain. The transcriptome analysis shows that 63% (n=12629) of all mouse one-to-one human orthologue genes (n=16320) are expressed in the basal ganglia and 183 genes show an elevated expression in basal ganglia compared to other regions of the brain.
Table 3: Number of genes within the different categories of regionally elevated expression, in mouse basal ganglia.
Elevated expression in basal ganglia compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in basal ganglia compared to all other regions), group enriched (at least four-fold higher mRNA levels in a group of 2-5 regions) and regionally enhanced (at least four-fold higher mRNA levels in basal ganglia compared to the average of all regions), The number of genes in the individual category is shown in Table 3. In Table 4, the 12 genes with the highest level of regional specificity among the 48 enriched genes are listed.
Figure 3. Schematic drawing of the mouse brain, indicating the location of basal ganglia from a sagittal and coronal view. Table 4: The 12 genes with the highest level of enriched expression in mouse basal ganglia. "Predicted localization" shows the classification of each gene into three main classes: Secreted, Membrane, and Intracellular, where the latter consists of genes without any predicted membrane and secreted features. RS-score (Regional Specificity score) corresponds to the score calculated as the fold change to the second highest region.
Proteins specifically detected in mouse basal gangliaRegionally elevated protein expression in pigThe pig basal ganglia is similar to the human basal ganglia divided into striatum and pallidum, a collection of subcortical nuclei involved in movement control and processing. The sub regions included in this analysis are four different sub regional areas; caudate nucleus, putamen, septum and ventral pallidum. The transcriptome analysis shows that 66% (n=13274) of all pig genes (n=15829) are expressed in the cerebellum and 143 genes show an elevated expression in cerebellum compared to other regions of the brain. Table 5: Number of genes within the different categories of regionally elevated expression, in pig basal ganglia
Figure 4. Schematic drawing of the pig brain, indicating the location of basal ganglia from a sagittal view. . Elevated expression in basal ganglia compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in basal ganglia compared to all other regions), group enriched (at least four-fold higher mRNA levels in a group of 2-5 regions) and regionally enhanced (at least four-fold higher mRNA levels in basal ganglia compared to the average of all regions), The number of genes in the individual category is shown in Table 1. In Table 2, the 12 genes with the highest level of regional specificity among the 41 enriched genes are listed. Table 6: The 12 genes with the highest level of enriched expression in pig basal ganglia. "Predicted localization" shows the classification of each gene into three main classes: Secreted, Membrane, and Intracellular, where the latter consists of genes without any predicted membrane and secreted features. RS-score (Regional Specificity score) corresponds to the score calculated as the fold change to the second highest region.
Extended informationLateral ventricle wallCaudate nucleus is a brain region close to the lateral ventricle, which means that although the ventricle wall is not part of the basal ganglia it is often included in the sampling of caudate nucleus, and we are able to see both RNA expression related to location specific cell types as well as proteins with a specific relation to the ependymal cells or subventricular zone.
Extended human basal ganglia tissue sectionA limited number of targets are selected for a more extensive profiling in human brain, providing a better overview of the regional location in the region of interest. Such is the case for SLC6A3, a protein specifically expressed in Substantia nigra but then transported into caudate nucleus and show variation within the caudate nucleus.
The standard setup in the Tissue Atlas, profiling human tissues, is based on Tissue Micro array technique, saving valuable tissue material as well as reagents but still providing a good tissue representation for protein profiling. However, due to the complex nature of the brain, with different cell types and subfields, sometimes a larger tissue sample is needed to fully understand the protein location. In table 7 the selected targets used for protein profiling on extended tissue material are listed. Table 7. The following 46 genes have been analyzed using extended basal ganglia samples. |
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The Human Protein Atlas
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