Pons and Medulla oblongata

Pons and medulla oblongata together with midbrain and thalamus are part of the brainstem, which is located in the posterior part of the brain. It is a region of transition between central and peripheral nervous system, containing cell nuclei of majority of cranial nerves from which they are emerging to the spinal cord. The pons and medulla developmentally originate from the third vesicle of neural tube (rhombencephalon). Hox genes orchestrate the segmented organization of spinal cord, pons and medulla and are not expressed in other parts of the brain. Pons facilitates connections between medulla and cerebellum, as well as into the thalamus. Medulla receives inputs from pyramidal tracts originating from the cerebral cortex. These nerves are involved in control of the motoric functions. An important function of pons and medulla is the autonomous control of the body's vital functions. For example the cardiovascular (medulla) centers receive sensory inputs from the heart and blood vessels (mechano-, baro- and chemoreceptors) via the vagus nerve and modulates heart rate and blood pressure. A complex network between antagonistic respiratory (pons & medulla) centers regulates the pattern and rate of the respiratory cycle of inhalation and exhalation.

Figure 1. Schematic drawing of the human brain, indicating the location of pons and medulla from a coronal perspective or sagittal view.


EMX2 - NTS

FEV - NTS


CALCA - n. ambiguus

ADCYAP1 - parabrachial n.

The transcriptome analysis shows that 85% (n=16774) of all human protein-coding genes (n=19670) are expressed in the human pons and medulla. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 11777 of all mouse one-to-one orthologues (n=15160) are expressed in the mouse pons and medulla and that 12452 of all pig orthologues (n=14656) are expressed in the pig pons and medulla.

Gene classification based on regional RNA expression in human, pig and mouse pons and medulla defines 200 genes as pons and medulla enriched in either of the three species, and 34 out of those genes show highest expression levels in pons and medulla in all three species.

Neurotransmitter systems in pons and medulla oblongata

Noradrenalin

Noradrenalin belongs to the monoamine family of neurotransmitters. It is a hormone and neurotransmitter that increases body arousal and reaches high levels during stress (sympathetic system). The locus coeruleus (LC) located near the 4th ventricle, is the major site of Noradrenalin synthesis in the brain. The LC neurons have projections to all regions of the brain, modulating the arousal state of the brain. Example enzymes involved in noradrenalin synthesis and noradrenalin transport can be found below.


TH - LC

SLC6A2 - LC

SLC6A2 - projections


Glycine

Glycine is the simplest amino acid, with the hydrogen atom as a side chain.
In the brain. Glycine acts as an inhibitory neurotransmitter predominantly in the brain stem, spinal cord and retina, where activation of glycine receptors causes influx of chloride ions.

Acetylcholine

Acetylcholine is an excitatory neurotransmitter that in the brain has a role in the arousal, plasticity and reward. The pons and medulla oblongata contain several populations of cholinergic neurons. These include groups of motor neurons that regulate facial expression and eye movements. In addition, the pons contains populations of cholinergic projection neurons that innervate other parts of the brain including thalamus, hypothalamus and midbrain.


SLC18A3

SLC18A3

Regionally elevated expression in human

The transcriptome analysis shows that 85% (n=16774) of all human proteins (n=19670) are expressed in the Pons and medulla. 393 genes show an elevated expression level in cerebellum compared to other regions of the brain.

  • 174 regionally enriched genes
  • 393 regionally elevated genes in total
  • 224 of the pons and medulla elevated genes are elevated in other tissues than the brain.
  • 169 of the pons and medulla elevated genes are elevated in the brain.


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

Specificity Number of Human elevated genes
Region enriched 174
Group enriched 133
Region enhanced 86
Elevated 393

Elevated expression in pons and medulla compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in pons and medulla 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 and medulla 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 174 enriched genes are listed.

Table 2. The 12 genes with the highest level of enriched expression in human cerebellum. "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
PHOX2B Paired like homeobox 2b Intracellular 99
PHOX2A Paired like homeobox 2a Intracellular 96
HOXB8 Homeobox B8 Intracellular 82
UPK3B Uroplakin 3B Intracellular,Membrane 58
CALCA Calcitonin related polypeptide alpha Secreted 48
HOXA5 Homeobox A5 Intracellular 46
DBH Dopamine beta-hydroxylase Intracellular 45
HOXA2 Homeobox A2 Intracellular 44
FBP2 Fructose-bisphosphatase 2 Intracellular 36
SLC6A4 Solute carrier family 6 member 4 Membrane 36
HOXB5 Homeobox B5 Intracellular 33
HPD 4-hydroxyphenylpyruvate dioxygenase Intracellular 29

Regionally elevated expression in mouse

Figure 2. Schematic drawing of the mouse brain, indicating the location of pons and medulla from a coronal perspective or sagittal view.

The transcriptome analysis shows that 60% (n=11777) of all mouse one-to-one human orthologue genes (n=15160) are expressed in the pons and medulla and 103 genes show an elevated expression in pons and medulla compared to other regions of the brain.

Table 3: Number of genes within the different categories of regionally elevated expression, in mouse pons and medulla

Specificity Number of Mouse elevated genes
Region enriched 39
Group enriched 46
Region enhanced 18
Elevated 103

Elevated expression in pons and medulla compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in pons and medulla 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 and medulla 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 39 enriched genes are listed.

Table 4: The 12 genes with the highest level of enriched expression in mouse pons and medulla. "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
HOXB5 Homeobox B5 Intracellular 90
HOXA5 Homeobox A5 Intracellular 88
HOXB6 Homeobox B6 Intracellular 60
HOXB8 Homeobox B8 Intracellular 48
HOXA4 Homeobox A4 Intracellular 47
HOXB7 Homeobox B7 Intracellular 45
HOXB3 Homeobox B3 Intracellular 40
HOXC5 Homeobox C5 Intracellular 40
HOXB4 Homeobox B4 Intracellular 36
HOXD3 Homeobox D3 Intracellular 36
HOXA2 Homeobox A2 Intracellular 35
HOXA6 Homeobox A6 Intracellular 34


PCP4L1

SLC10A4

CALCA

Regionally elevated expression in pig

The transcriptome analysis shows that 63% (n=12452) of all pig genes (n=14656) are expressed in pons and medulla and 78 genes show an elevated expression in pons and medulla compared to other regions of the brain.


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

Specificity Number of Pig elevated genes
Region enriched 26
Group enriched 46
Region enhanced 6
Elevated 78

Figure 3. Schematic drawing of the pig brain, indicating the location of pons and medulla from a coronal perspective or sagittal view .

Table 6: The 12 genes with the highest level of enriched expression in pig pons and medulla. "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
HOXB5 Homeobox B5 Intracellular 128
HOXA4 Homeobox A4 Intracellular 60
DBH Dopamine beta-hydroxylase Intracellular 38
HOXA3 Homeobox A3 Intracellular 34
HOXD3 Homeobox D3 Intracellular 32
SLC6A2 Solute carrier family 6 member 2 Intracellular,Membrane 32
HOXB2 Homeobox B2 Intracellular 29
HOXB3 Homeobox B3 Intracellular 29
HOXD4 Homeobox D4 Intracellular 28
HOXA2 Homeobox A2 Intracellular 27
PHOX2B Paired like homeobox 2b Intracellular 27
HOXB6 Homeobox B6 Intracellular 25