White matter Anatomical divisions Regionally elevated protein expression in human Regionally elevated protein expression in mouse Regionally elevated protein expression in pig Extended information

White matter

Summary

White matter consists of myelinated axons. It is present through out the brain and spinal cord as a tree of connectivity. The largest white matter structures is the corpus callosum which connects the two hemispheres allowing their signal end information exchange. Developmentally white matter emerges from the marginal layer of neuroblasts of the wall of the neuronal tube. White matter continues to develop during childhood and adolescence up to middle age. White matter allows signals to pass rapidly between different regions of the brain.

The transcriptome analysis shows that 83% (n=16727) of all human protein-coding genes (n=20162) are expressed in the human white matter (represented by RNA expression in white matter).

Gene classification based on regional RNA expression in human, pig and mouse white matter defines 8 genes as white matter enriched in either of the three species, and 3 out of those genes show highest expression levels in white matter in all three species.

Figure 1. Schematic drawing of the human brain, indicating the location of white matter from a sagittal perspective.

Anatomical divisions

The white matter samples in the brain section can be divided into cortical white matter, cerebellar white matter and spinal cord white matter. All these white matter structures express many genes associated with myelination, but also each have unique molecular features related to the location and types of neurons that use these nerve bundles to connect to other regions of the brain.

Regionally elevated protein expression in human

The transcriptome analysis shows that 83% (n=16727) of all human proteins (n=20162) are expressed in the white matter. 67 genes show an elevated expression level in white matter compared to other regions of the brain.

1 regionally enriched genes
67 regionally elevated genes in total
67 of the white matter elevated genes are elevated in other tissues than the brain.
20 of the white matter elevated genes are elevated in the brain.

Table 1: Number of genes within the different categories of regionally elevated expression, in human white matter.

Specificity	Number of Human elevated genes
Region enriched	1
Group enriched	53
Region enhanced	13
Elevated	67

Elevated expression in white matter compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in white matter 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 white matter compared to the average of all regions), The number of genes in the individual category is shown in Table 1. In Table 2, the 1 genes with high level of regional specificity are listed.

Table 2. The 1 genes with the highest level of enriched expression in human white matter. "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.

Gene	Description	Predicted location	RS-score
GARIN4	Golgi associated RAB2 interactor family member 4	Intracellular	5

Regionally elevated protein expression in mouse

The transcriptome analysis shows that 62% (n=12565) of all mouse one-to-one human orthologue genes (n=16679) are expressed in the white matter and 62 genes show an elevated expression in white matter compared to other regions of the brain.

Table 3: Number of genes within the different categories of regionally elevated expression, in mouse white matter

Specificity	Number of Mouse elevated genes
Region enriched	7
Group enriched	35
Region enhanced	20
Elevated	62

Table 4: The 7 genes with the highest level of enriched expression in mouse white matter. "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.

Gene	Description	Predicted location	RS-score
THBS4	Thrombospondin 4	Secreted, Intracellular	8
KRTDAP	Keratinocyte differentiation associated protein	Secreted	6
CLDN11	Claudin 11	Membrane	5
NKX6-2	NK6 homeobox 2	Intracellular	5
ALOX5	Arachidonate 5-lipoxygenase	Intracellular	4
CNP	2',3'-cyclic nucleotide 3' phosphodiesterase	Intracellular	4
GSN	Gelsolin	Secreted, Intracellular	4

Regionally elevated protein expression in pig

The transcriptome analysis shows that 68% (n=13612) of all pig genes (n=16614) are expressed in white matter and 4 genes show an elevated expression in white matter compared to other regions of the brain.

Table 5: Number of genes within the different categories of regionally elevated expression, in pig white matter.

Specificity	Number of Pig elevated genes
Region enriched	0
Group enriched	2
Region enhanced	2
Elevated	4

Extended information

The glial cells generating the myelin of the central nervous system white matter are called oligodendrocytes. In the peripheral nervous system, myelin is create by shwann cells.

MBP - cerebral cortex