The tongue-specific proteome
The tongue is a muscular organ located within the oral cavity responsible for the ability to swallow, taste and speak. It is composed of interlacing skeletal muscle, pockets of adipose and connective tissue covered in oral mucosa infused with numerous taste buds. The right and left sides of the tongue are separated by the lingual septum while the anterior and posterior parts are separated by the terminal sulcus. Located on the base of the posterior part of the tongue are the lingual tonsils. Transcriptome analysis shows that 61% (n=12306) of all human proteins (n=20090) are expressed in the tongue and 490 of these genes show an elevated expression in the tongue compared to other tissue types.
The tongue transcriptome
Transcriptome analysis of the tongue can be visualized with regard to the specificity and distribution of transcribed mRNA molecules (Figure 1). Specificity illustrates the number of genes with elevated or non-elevated expression in the tongue compared to other tissues. Elevated expression includes three subcategory types of elevated expression:
Distribution, on the other hand, visualizes how many genes have, or do not have, detectable levels (nTPM≥1) of transcribed mRNA molecules in the tongue compared to other tissues. As evident in Table 1, all genes elevated in tongue are categorized as:
Figure 1. (A) The distribution of all genes across the five categories based on transcript specificity in tongue as well as in all other tissues. (B) The distribution of all genes across the six categories, based on transcript detection (nTPM≥1) in tongue as well as in all other tissues.
Table 1. The number of genes in the subdivided categories of elevated expression in tongue.
Gene expression shared between tongue and other tissues
There are 232 group enriched genes expressed in tongue. Group enriched genes are defined as genes showing a 4-fold higher average level of mRNA expression in a group of 2-5 tissues, including tongue, compared to all other tissues.
To illustrate the relation of tongue tissue to other tissue types, a network plot was generated, displaying the number of genes with a shared expression between different tissue types.
Figure 2. An interactive network plot of the tongue enriched and group enriched genes connected to their respective enriched tissues (grey circles). Red nodes represent the number of tongue enriched genes and orange nodes represent the number of genes that are group enriched. The sizes of the red and orange nodes are related to the number of genes displayed within the node. Each node is clickable and results in a list of all enriched genes connected to the highlighted edges. The network is limited to group enriched genes in combinations of up to 5 tissues, but the resulting lists show the complete set of group enriched genes in the particular tissue.
Tongue shares most group enriched gene expression with skeletal muscle. It also shares group enriched gene expression with the heart, liver, brain, testis and adrenal gland.
A major part of tongue tissue consists of muscle fibers also present in the heart and skeletal muscle. This explains the expression of genes like; Actinin alpha 2 ACTN2, Myomesin 1 MYOM1, and Sarcalumenin SRL. Other genes shared between tongue and other organs are for example NOX1 in brain, GOT1 in liver and CPT1B in testis.
Tongue anatomy and function
The tongue is a muscular organ mainly composed of skeletal muscle located in the oral cavity responsible for the ability to swallow, taste and speak. It is composed of interlacing skeletal muscle, pockets of adipose and connective tissue (with mucus and serous glands) covered in oral mucosa.
As previously mentioned the human tongue is composed of eight muscles; 4 intrinsic and 4 extrinsic, and attached to the hyoid bone, mandible, styloid process, palate and pharynx. Furthermore, the tongue is often divided into sections. The right and left side of the tongue are separated by a section of fibrous tissue known as the lingual septum. It is further divided into an anterior and posterior part which are structurally and developmentally distinct. The dorsal surface of the anterior part makes up roughly two-thirds of tongue length while the posterior part consists of the remaining one-third. The anterior two-thirds of the tongue consists of a type of oral mucosa called masticatory mucosa which is made up by keratinized stratified squamous epithelium.. Embedded in the masticatory mucosa are numerous lingual papillae containing taste buds and taste receptors. The ventral surface of the anterior tongue consists of smooth stratified squamous non-keratinized epithelium. Located here are the lingual tonsils which are a collection of nodular lymphatic tissue.
The papillae on the anterior tongue come in four types; filiform, fungiform, foliate and circumvallate. The filiform papillae are the most numerous and cover all of the anterior of the tongue’s surface. They are small cone-shaped structures with keratinized epithelial prolongations which give the tongue its typical texture and which contain many nerves. They are the only papillae not containing any taste buds. Fungiform papillae are mushroom-shaped, nonkeratinized projections, situated mainly on the tip of the tongue, with taste buds on the upper surface. Lastly, there are the foliate papillae which are leaf-shaped and reside on the posterior edges of the tongue. Far back on the anterior two-thirds of the tongue, lining the terminal sulcus, are 3-13 circumvallate papillae. These 1-2mm big papillae are shaped like a dome surrounded by a horseshoe-shaped cleft. The cleft is lined with taste buds and in the bottom, the ducts from the von Ebner’s glands empty their contents. Von Ebner’s gland secretion contains lingual lipase which starts the hydrolysis of lipids in the mouth as well as flushes material from the taste buds to enable fast response to changing stimuli.
As mentioned, located on the base of the posterior part of the tongue are the lingual tonsils. These tonsils are two small aggregations of lymphatic tissue that assist the immune system in the production of antibodies in response to invading pathogens. A thin capsule of connective tissue separates them from adjacent structures.The surface of the tonsils is covered by stratified squamous non-keratinized epithelium and has pits that lead to the lower lymphatic tissue. Contrary to the palatine- and pharyngeal tonsils, the lingual tonsils do not often get inflamed. This is due to mucus glands located at the root of the tongue which drains into their crypt. These secretions from the mucous glands help keep the crypt clean and make them less prone to infection.
Here, the protein-coding genes expressed in tongue are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize corresponding protein expression patterns of genes with elevated expression in tongue.
Transcript profiling was based on a combination of two transcriptomics datasets (HPA and GTEx), corresponding to a total of 14590 samples from 54 different human normal tissue types. The final consensus normalized expression (nTPM) value for each tissue type was used for the classification of all genes according to the tissue-specific expression into two different categories, based on specificity or distribution.
Relevant links and publications
Uhlén M et al., Tissue-based map of the human proteome. Science (2015)