1), different taxa have likely evolved divergent strategies of regeneration and warrant further study. Given the variation in size, shape, and tissues (Fig. Rather, mammals can regenerate tissues such as skeletal muscle or peripheral nerves, but the majority of mammalian tissues or organs cannot be replaced (Fig. Whereas zebrafish, axolotls, and larval Xenopus frogs are capable of regrowing structures nearly identical to the original appendage and adult Xenopus frogs and lepidosaurs exhibit non-identical regeneration, mammals do not replace lost appendages (Fig. On the other hand, regenerative capacity of vertebrate appendages varies extensively and can be viewed as a spectrum of abilities. Processes such as a diminished injury response, specialized wound epidermis formation, extracellular matrix remodeling, reinnervation, and reactivation of conserved developmental pathways are shared across regeneration-enabled vertebrates 37– 39, indicating a conserved program that is likely altered or shut down in mammals. In mammals, it is hypothesized that the loss of regenerative capacity may be related to the development of a specialized immune system 33, 34, increased regulation of the cell cycle 35, or the evolution of endothermy 36. In these instances, regenerative capacity may be lost as a neutral trait or by negative selection as a trade-off of energy allocation, reproduction, or developmental growth 32. While regeneration is selectively advantageous, closely-related taxa can demonstrate a wide range of regenerative abilities, including some with limited or no capacity. However, the regeneration of lost structures can mitigate these costs by recovering partial or full function of the original structure 21, 28, 30, 31. While an obvious advantage of autotomy is immediate survival, the absence of a fin, limb, or tail can have severe repercussions for an individual, as these structures are essential for locomotion and balance, energy storage, sexual selection, and defense 23– 29. Moreover, skin autotomy has also been reported in a rodent, the African spiny mouse 22. As a result, some species of salamanders and lizards evolved the ability to autotomize, or self-amputate, the tail as an evasive defense tactic 13– 21. Among vertebrates, sublethal predation is common among natural populations of teleost fish, anuran tadpoles, urodele amphibians, and non-avian reptiles 7– 12. Selective pressures are driving forces of trait evolution, and within some, but not all taxa, predation pressures are likely associated with the maintenance of regenerative abilities. As a result, many researchers are dedicated to understanding the mechanisms, as well as evolutionary pressures, that enable structural regeneration in different vertebrate taxa, which can be utilized to enhance or improve wound healing outcomes in mammals. Compared to normal tissue, scar tissue has reduced functionality, decreased sensitivity, and greater risk of infection 6. In contrast to regeneration-enabled vertebrates, the mammalian injury response is characterized by slow, wound healing and repair of damaged tissues 5. Among amniotes, non-avian reptiles are the only group known to regenerate complex, multi-tissue structures such as the tail 1– 4, whereas mammals and birds exhibit a very limited capacity for regeneration as adults. Overall, this study of wild-caught, juvenile American alligator tails identifies a distinct pattern of wound repair in mammals while exhibiting features in common with regeneration in lepidosaurs and amphibia.Īppendage regeneration is widespread among vertebrate groups and anamniotes, such as the zebrafish, Xenopus, and axolotl, have long been the focus of regenerative studies. The lack of skeletal muscle contrasts with lizards, but shares similarities with regenerated tails in the tuatara and regenerated limbs in Xenopus adult frogs, which have a cartilaginous endoskeleton surrounded by connective tissue, but lack skeletal muscle. The overproduction of connective tissue shares features with mammalian wound healing or fibrosis. Furthermore, the regrown alligator tail lacked skeletal muscle and instead consisted of fibrous connective tissue composed of type I and type III collagen fibers. This contrasts with lepidosaurs, where the regenerated tail is radially organized around a central endoskeleton. Gross dissection, radiographs, and magnetic resonance imaging revealed that caudal vertebrae were replaced by a ventrally-positioned, unsegmented endoskeleton. The regrown alligator tails constituted approximately 6–18% of the total body length and were morphologically distinct from original tail segments. This study presents the first anatomical and histological evidence of tail repair with regrowth in an archosaur, the American alligator. Reptiles are the only amniotes that maintain the capacity to regenerate appendages.
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