The lower jaw is a crucial in everyday functions, such as chewing and communication as well as being an aesthetically important part of the face. Resection owing to cancer treatment or injury may result in the loss of jaw parts, affecting the patient's quality of life. Jaw restoration surgery is often technically challenging, which drives interest in new therapeutic strategies. One research approach for this is to investigate highly regenerative processes in model organisms that are known to be able to fully regenerate their amputated limbs – such as the axolotl.
For their study, Kramer, Aires, Sandoval-Guzmán and colleagues removed part of the axolotl's lower jaw, including skin, muscle, oral mucosa and connective tissue, and observed the regeneration process over 90 days. The authors also performed RNA sequencing to determine the change in gene expression patterns and their corresponding actions in the regenerating tissue. During the early stages of regeneration, the authors observed wound closure and the expression of genes connected with muscle contraction and maturation. By 14 days post injury (dpi) the site of injury had significantly reduced, yielding a blastema, i.e. the aggregation of cells with the ability to differentiate into different body parts. The authors determined that, at this stage, the regenerating lower jaw tissues strongly expressed genes related to cell adhesion and migration, extracellular matrix disassembly and organisation, and immune response. After 35 dpi, the defect was visually undetectable, and genes related to cartilage formation, intramembranous ossification and regeneration of blood vessels were found to be upregulated. At 35 dpi, the perimeter of the regenerated lower jaw was just 9.2% smaller than the intact control at 90 dpi and contained regenerated teeth.
The authors then compared their RNA sequencing data obtained from the regenerating mandible with previously published data relating to the regenerating limb of the axolotl. They found that ∼70% of genes present in lower jaw regenerating tissues was also present in regenerating limb tissues, especially during early and mid-stages of regeneration, thereby indicating common regenerative mechanisms within body parts of different embryonic origin in axolotl.
This study highlights key mechanisms of regeneration in the highly regenerative model organism, the axolotl. It provides insight regarding limitations of limb regeneration in humans, and points to potential therapeutic targets for regenerative medicine.
