Amphibians are an interesting clade for the study of regenerative medicine. Whereas most other tetrapods are unable to regenerate lost limbs, some amphibians can. Throughout their lives, urodeles (newts and salamanders) are able to regenerate the complete structure of a lost limb in a smaller but fully functioning replacement. Juvenile anurans (frogs and toads) have a similar ability during the larval stage, but adults only regenerate 'spikes' or cartilaginous rods that lack the joints and structure of the lost limb. This is the case with adult Xenopus laevis, the African clawed frog that has become a popular model for biomedical research.

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Because anurans show this incomplete regeneration in adulthood, they are considered an intermediate model between the complete regenerative ability of urodeles and the absence of regenerative ability in mammals. Researchers, including Rio Tsutsumi and colleagues at Kyoto University (Japan), hope that by achieving functional limb regeneration in frogs they can help bridge the gap between regenerative amphibians and non-regenerative tetrapods, such as humans. Building upon previous work that described the regeneration of amputated joints in a species of newt, Tsutsumi's team hypothesized that an adult frog might be able to regenerate a complete elbow joint under specific circumstances. The researchers amputated limbs at the elbow and studied the cartilaginous spike that grew in its place. Although they had removed the distal side of the elbow joint, frogs were able to bend and stretch the regenerated forelimb at the elbow (Regeneration doi:10.1002/reg2.49; published online 6 January 2016).

Using epifluorescence image capture, Tsutsumi et al. were able to reconstruct three-dimensional images that demonstrated the structure of this regenerated limb and the concave, socket-like morphology of the regenerated joint. They also observed in these images that the major flexor and extensor muscles (the biceps and triceps, respectively) inserted into the regenerated spike in a pattern than resembled that of the intact forelimb. Together these findings suggest that a functional elbow structure was regenerated at the elbow-end of the spike cartilage.

To explain these findings, the researchers propose that regeneration depends upon interactions between remaining tissues and the regenerating tissues. Such interactions guide the growth and integration of regenerated tissues into remaining tissues in a process that Tsutsumi et al. call 'reintegration'. By further studying these interactions and the process of reintegration, the scientists hope to unravel the mechanisms that allow functional regeneration in vertebrate species.