Medulla oblongata

Medulla oblongata is situated inferior to the pons. It connects to the pons superiorly, and to the spinal cord inferiorly. The medulla oblongata together with pons, midbrain and thalamus comprise the brainstem. Developmentally, medulla oblongata originates from the third vesicle of the neuronal tube (rhombencephalon). 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. Medulla oblongata receives inputs from pyramidal tracts originating from the cerebral cortex and these nerves are involved in the control of motor functions. An important function of pons and medulla is the autonomous control of the body's vital functions. For example, modulating heart rate and blood pressur based on input from the cardiovascular centers which receive sensory inputs from the heart and blood vessels (mechano-, baro- and chemoreceptors) via the vagus nerve.

The transcriptome analysis shows that 83% (n=16792) of all human protein-coding genes (n=20162) are expressed in the human medulla oblongata. Human one-to-one orthologues were investigated in pig and mouse brain, suggesting that 12587 of all mouse one-to-one orthologues (n=16679) are expressed in the mouse medulla oblongata and that 13995 of all pig orthologues (n=16614) are expressed in the pig medulla oblongata.

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

Gene classification based on regional RNA expression in human, pig and mouse medulla oblongata defines 7 genes as medulla oblongata enriched in either of the three species, and 0 out of those genes show highest expression levels in medulla oblongata in all three species. .

Anatomical division

Medulla oblongata can be divided into a pyramidal part and the tegmentum. The pyramidal part contains regions such as the corticospinal tract. The tegmentum of medulla oblongata encompasses several areas related to autonomic function such as the nucleus tractus solitarii which is the grey matter nucleus of the solitary tract (which contains nerve fibres from the vagal, facial, and hypoglossal cranial nerves). It receives input from mechano- and chemoreceptors of the heart and respiratory system via the vagal and glossopharyngeal nerve and projects to several regions including hypothalamus and amygdala. There are also efferent nuclei within tegmentum of medulla oblongata e.g., the dorsal motor vagal complex of the tenth cranial nerve, the prepositus hypoglossal nucleus and the motor hypoglossal nucleus of the twelfth cranial nerve. Medulla oblongata also contains the nucleus ambiguous that is crucial for bulbar reflexes such as swallowing while it also situates several nuclei responsible for sensory relay such as the nucleus cuneatus and nucleus gracilis.


SLC18A3 - dorsal motor nu. of vagus and hypoglossal nu.

The tegmentum of medulla oblongata also situates several raphe nuclei such as the nucleus raphe magnus, nucleus raphe obscurus and nucleus raphe pallidus. These nuclei contain groups of serotonergic neurons which are modulated by the midbrain. These nuclei are involved in pain regulation, motor function of respiration and immunoreactions such as fever, respectively. Other parts of the tegmentum are the gigantocellular reticular nuclei, medullary and the gigantocellular reticular nuclei, pars. These are part of the medullary reticular formation and are involved in respiratory expiration together with the parvicellular reticular nuclei and parvicellular reticular nuclei, medullary.

Regionally elevated expression in human

The transcriptome analysis shows that 83% (n=16792) of all human proteins (n=20162) are expressed in the medulla. 90 genes show an elevated expression level in medulla compared to other regions of the brain.

  • 6 regionally enriched genes
  • 90 regionally elevated genes in total
  • 78 of the medulla oblongata elevated genes are elevated in other tissues than the brain.
  • 12 of the medulla oblongata elevated genes are elevated in the brain.


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

Specificity
Number of Human elevated genes
Region enriched 6
Group enriched 57
Region enhanced 27
Elevated 90

Elevated expression in medulla oblongata compared to other brain regions is divided into three different categories; regionally enriched (at least four-fold higher mRNA levels in medulla oblongata 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 medulla oblongata compared to the average of all regions), The number of genes in the individual category is shown in Table 1. In Table 2, the 6 enriched genes are listed.

Table 2. The 6 enriched genes in medulla oblongata. "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
GCG Glucagon Secreted 51
CRH Corticotropin releasing hormone Secreted 6
BHLHE23 Basic helix-loop-helix family member e23 Intracellular 5
FOXD3 Forkhead box D3 Intracellular 4
IGLV3-9 Immunoglobulin lambda variable 3-9 Secreted 4
IGLV4-69 Immunoglobulin lambda variable 4-69 Secreted 4

Regionally elevated expression in mouse

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

Regionally elevated expression in pig

The transcriptome analysis shows that 69% (n=13995) of all pig genes (n=16614) are expressed in medulla oblongata and 37 genes show an elevated expression in medulla compared to other regions of the brain.


Table 3: Number of genes within the different categories of regionally elevated expression, in pig medulla oblongata.

Specificity
Number of Pig elevated genes
Region enriched 1
Group enriched 28
Region enhanced 8
Elevated 37

Figure 2. Schematic drawing of the pig brain, indicating the location of medulla oblongata from a sagittal view.

Table 4: The 1 gene with the highest level of enriched expression in pig 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
PRLH Prolactin releasing hormone Secreted 14

Extended information