Tongue Muscle for the Analysis of Head Muscle Regeneration Dynamics

Abstract

Tongue muscle damage impairs speaking and eating, thereby degrading overall health and quality of life. Skeletal muscles of the body are diverse in embryonic origin, anatomic location, and gene expression profiles. Responses to disease, atrophy, aging, or drugs vary among different muscles. Currently, most muscle studies are focused on limb muscles and the tongue is neglected. The regenerative ability of tongue muscle remains unknown, and thus there is need for tongue muscle research models. Here, we present a comprehensive characterization of the spatiotemporal dynamics in a mouse model of tongue muscle regeneration and establish a method for the isolation of primary tongue-derived satellite cells. We compare and contrast our observations with the tibialis anterior (TA) limb muscle. Acute injury was induced by intramuscular injection of cardiotoxin, a cytolytic agent, and examined at multiple timepoints. Initially, necrotic myofibers with fragmented sarcoplasm became infiltrated with inflammatory cells. Concomitantly, satellite cells expanded rapidly. Seven days postinjury, regenerated myofibers with centralized nuclei appeared. Full regeneration, as well as an absence of fibrosis, was evident 21 d postinjury. Primary tongue-derived satellite cells were isolated by enzymatic separation of tongue epithelium from mesenchyme followed by magnetic-activated cell sorting. We observed that tongue displays an efficient regenerative response similar to TA but with slightly faster kinetics. In vitro, tongue-derived satellite cells differentiated robustly into mature myotubes with spontaneous contractile behavior and myogenic marker expression. Comparison of gene expression signatures between tongue and TA-derived satellite cells revealed differences in the expression of positional-identity genes, including the HOX family. In conclusion, we have established a model for tongue regeneration useful for investigations of orofacial muscle biology. Furthermore, we showed that tongue is a viable source of satellite cells with unique properties and inherited positional memory.

New Approach to Addison Disease: Oral Manifestations Due to Endocrine Dysfunction and Comorbidity Burden

“…Recently, tongue analysis has been the subject of interesting clinical and preclinical studies concerning general autoimmune conditions [ 45 , 46 ]. This muscle represents a frequently neglected subject of examination, yet it has a major role in daily life due to its involvement in eating, speech, and thus in overall QL [ 45 , 46 ].…”

“…Recently, tongue analysis has been the subject of interesting clinical and preclinical studies concerning general autoimmune conditions [ 45 , 46 ]. This muscle represents a frequently neglected subject of examination, yet it has a major role in daily life due to its involvement in eating, speech, and thus in overall QL [ 45 , 46 ]. Tongue evaluation is part of the orofacial assessment in patients with AD on first admission or during follow-up for adrenal disease [ 45 , 46 , 47 , 48 ] ( Figure 3 ).…”

“…Even in apparently healthy subjects with an irrelevant general clinical exam and negative medical family history who are admitted for patchy changes in tongue color, the index of suspicion regarding AD should not be dismissed [ 45 , 46 , 47 , 48 ]. The pigmented lingual patches may be single or multiple; they are situated at the level of dorsal and lateral areas, either isolated or synchronous with similar lesions at other anatomical parts such as lips and palatine arches [ 45 , 46 , 47 , 48 ]. In addition to hormonal imbalance-related pigmentation, fungiform pigmented papillae are reported in AD individuals [ 49 , 50 , 51 ].…”

Physiology of the tongue with emphasis on taste transduction

“…Given that the mature tongue consists of a variety compartmentalized tissue types, it is not surprising that it is derived from several different cell populations within the embryo. The lingual muscles are of mixed origin deriving from myoblasts originating in the most anterior set of somites, the occipital somites, and are labeled by the transcription factors mesoderm posterior BHLH transcription factor 1 (MesP1) and the paired box transcription factors Pax3 and Pax7 ( 188 – 194 ) and from the cranial paraxial mesoderm ( 195 ). Pax3 is essential for the expansion of the pool of lingual myogenic progenitors at around embryonic day 10 (E10) ( 196 ).…”

“…Muscle regeneration is mainly orchestrated by a population of muscle stem cells, termed satellite cells (MuSCs). As tongue MuSCs are of the Mesp1/Pax3/Pax7 lineage, they share more in common with limb muscles ( 193 , 194 , 205 , 206 ) than do the other craniofacial muscles, which are of different lineages. A recent report compared the regenerative potential of tongue muscle and tibialis anterior (TA) limb muscle in response to acute injury by intramuscular injection of cardiotoxin, a cytolytic agent ( 194 ).…”