Pons Anatomical divisions Regionally elevated expression in human Regionally elevated expression in mouse Regionally elevated expression in pig Extended information

Pons

Summary

Pons is situated inferior to the midbrain, superior to the medulla oblongata and ventral to the fourth ventricle. The pons together with medulla oblongata, midbrain and thalamus comprise the brainstem. Developmentally the pons originates from the third vesicle of the neuronal tube (rhombencephalon). There are several monoamine nuclei situated in the pons, such as noradrenergic locus coeruleus. Hox genes are the "blue-print genes" that orchestrate the segmented organization of spinal cord, pons and medulla, and they are only expressed in pons and medulla oblongata. Pons facilitates connections between medulla and cerebellum, as well as into the thalamus and is important for the control of several of the body’s vital functions. Regulation of the pattern and rate of the respiratory cycle is managed by pons together with the medulla oblongata through a complex network between antagonistic respiratory centres.

The transcriptome analysis shows that 72% (n=14546) of all human protein-coding genes (n=20090) are expressed in the human pons. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 12331 of all mouse one-to-one orthologues (n=16320) are expressed in the mouse pons and that 12943 of all pig orthologues (n=15829) are expressed in the pig pons.

Gene classification based on regional RNA expression in human, pig and mouse pons defines 5 genes as pons enriched in either of the three species, and 0 out of those genes show highest expression levels in pons in all three species.

Figure 1. Schematic drawing of the human brain, indicating the location of pons from a sagittal view.

Anatomical divisions

Pons can be divided into a basilar (ventral) part and the pontine tegmentum (dorsal). The basilar division includes the pontine nuclei, a group of several nuclei that are involved in motor function. The cranial nerves trigeminal- (V), abducens- (VI), facial- (VII), and vestibulocochlear (VIII) connect to the pons. Within pontine tegmentum, some nuclei of the cranial nerves are located e.g., the efferent motor facial nucleus and motor trigeminal nucleus and the afferent dorsal cochlear nucleus; posteroventral cochlear nucleus; anterior cochlear nucleus, ventral; principal sensory trigeminal nucleus; spinal trigeminal nucleus, oral; superior vestibular nucleus; and lateral vestibular nucleus. These nerves and nuclei are important for functions such as transmission of sensory information, movement of face and eyes, proprioception, and hearing.

GLRA1 - p. sensory n. of the trigeminal
SLC18A3 - motor trigeminal n.
PCP4L1 - cochlear n.
SLC10A4 - facial motor n.

Within the pontine tegmentum, several regions reside that are important for auditory function. For example, the nuclei of the trapezoid body and the superior olive which are a part of the ascending and descending auditory pathway and manage several auditory related functions e.g., the localization of sound, together with the lateral lemniscus nuclei. The superior olive includes areas such as the medial olivary nucleus, medial periolivary nuclei, and the ventral periolivary nuclei. Other nuclei within the pontine tegmentum are the pontine raphe nucleus which contains the serotonergic B5 group of the monoaminergic cell groups defined by Dahlström A, Fuxe K. (1964). The pons situates several monoaminergic groups of cells (as does the midbrain and medulla oblongata) such as the noradrenergic cell groups ventrolateral tegmental area (A5), locus coeruleus (A6) and the subcoeruleus area (A7). The nucleus locus coeruleus is located near the 4th ventricle, right next to the subcoeruleus area. It manages wakefulness and attention and is implicated in Alzheimer’s disease. Noradrenalin is a hormone and neurotransmitter that increases body arousal, and reaches high levels during stress (sympathetic system). The locus coeruleus is the major site of noradrenaline synthesis in the brain and its neurons have projections to all regions of the brain, modulating the brains arousal state.

TH - Locus coeruleus
SLC6A2 - Locus coeruleus

The dorsal tegmental nucleus and the dorsolateral tegmental nucleus are also situated close to the fourth ventricle in the pontine tegmentum. They are involved in spatial navigation and attention modulation, respectively. Another part of the pons pontine tegmentum is the pontine reticular formation. It includes areas such as lateral parabrachial nucleus; medial parabrachial nucleus; paramedian reticular nucleus; reticular pontine nucleus, caudal; reticular pontine nucleus, oral, and reticulotegmental nucleus. They are involved in several functions, for instance, sleep. Also, the parabrachial nuclear complex and the Kölliker-Fuse nucleus are main areas in the pontine part of the lateral respiratory column. The lateral respiratory column also entails sub-regions within the medulla oblongata and are important for breathing and motor behaviour.

ADCYAP1 - parabrachial n.

Regionally elevated expression in human

The transcriptome analysis shows that 72% (n=14546) of all human proteins (n=20090) are expressed in the pons. 83 genes show an elevated expression level in pons compared to other regions of the brain.

4 regionally enriched genes
83 regionally elevated genes in total
45 of the pons elevated genes are elevated in other tissues than the brain.
38 of the pons elevated genes are elevated in the brain.

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

Specificity	Number of Human elevated genes
Region enriched	4
Group enriched	65
Region enhanced	14
Elevated	83

Elevated expression in pons compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in pons 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 pons compared to the average of all regions), The number of genes in the individual category is shown in Table 1. In Table 2, the 4 enriched gene is listed.

Table 2. The 4 gene with the highest level of enriched expression in human pons. "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
SLC6A2	Solute carrier family 6 member 2	Intracellular,Membrane	10
PHOX2A	Paired like homeobox 2A	Intracellular	9
DBH	Dopamine beta-hydroxylase	Intracellular	8
EXD1	Exonuclease 3'-5' domain containing 1	Intracellular	4

Regionally elevated expression in mouse

For RNAseq, mouse pons and medulla oblongata samples were combined. For more information about the mouse pons click pons and medulla oblongata in mouse.

Regionally elevated expression in pig

The transcriptome analysis shows that 64% (n=12943) of all pig genes (n=15829) are expressed in pons and 39 genes show an elevated expression in pons compared to other regions of the brain.

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

Specificity	Number of Pig elevated genes
Region enriched	3
Group enriched	32
Region enhanced	4
Elevated	39

Figure 3. Schematic drawing of the pig brain, indicating the location of pons from a sagittal view.

Table 6: The 3 genes with the highest level of enriched expression in pig pons. "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
DBH	Dopamine beta-hydroxylase	Intracellular	26
SLC6A2	Solute carrier family 6 member 2	Intracellular,Membrane	19
RLN3	Relaxin 3	Secreted	9

Extended information

Within the pons resides the locus coeruleus, a nucleus of approximately 40,000 neurons that is the major distributor of noradrenaline in the brain. This region has been implicated in Alzheimer's disease, already in early stages of the disease as described by the Braak stages.

This movie shows the presence and location of amyloid beta plaques and tau tangles in the locus coeruleus and cortex with Alzheimer´s disease. Interview: Prof Tomas Hökfelt, Karolinska Institutet.