Abstract
While most tetrapods are unable to regenerate severed body parts, amphibians display a remarkable ability to regenerate an array of structures. Frogs can regenerate appendages as larva, but they lose this ability around metamorphosis. In contrast, salamanders regenerate appendages as larva, juveniles, and adults. However, the extent to which fundamental traits (e.g., metamorphosis, body size, aging, etc.) restrict regenerative ability remains contentious. Here we utilize the ability of normally paedomorphic adult axolotls (Ambystoma mexicanum) to undergo induced metamorphosis by thyroxine exposure to test how metamorphosis and body size affects regeneration in age‐matched paedomorphic and metamorphic individuals. We show that body size does not affect regeneration in adult axolotls, but metamorphosis causes a twofold reduction in regeneration rate, and lead to carpal and digit malformations. Furthermore, we find evidence that metamorphic blastemal cells may take longer to traverse the cell cycle and display a lower proliferative rate. This study identifies the axolotl as a powerful system to study how metamorphosis restricts regeneration independently of developmental stage, body size, and age; and more broadly how metamorphosis affects tissue‐specific changes.
Highlights
The ability of some animals to regenerate missing body parts has fascinated scientists for centuries, and the clinical value of tissue regeneration has driven this topic to the forefront of current scientific inquiry (Davenport 2005)
We first identified morphological changes that occur in limbs due to thyroxine-induced metamorphosis using an agematched cohort of 44 young adult axolotls that varied across a broad range of body sizes (Fig. 1A and B)
We found that pre- and postmetamorphic limb skeletons were both ossified (Fig. 1C−F) and that there was no difference in the proportion of the limb occupied by muscle, skin, and skeletal components near the amputation plane (Fig. S1B and C)
Summary
The ability of some animals to regenerate missing body parts has fascinated scientists for centuries, and the clinical value of tissue regeneration has driven this topic to the forefront of current scientific inquiry (Davenport 2005). Appendage regeneration is deficient or absent in most extant vertebrates This begs the question: what factors constrain regeneration in some animals? A great deal of research has been aimed at understanding the cellular and molecular mechanisms of regeneration, few studies have addressed how fundamental organismal traits such as body size, age, or stage of the life-cycle may affect regenerative ability. Interpreting how these factors influence regeneration in some species could reveal the key cellular and molecular mechanisms that could promote regeneration in other animals. Cells are stimulated to reenter the cell cycle (Globus et al 1980) and accumulate to form a blastema, a mass of lineage-restricted progenitor cells that will eventually replace the missing limb
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