AR Highlights

Abstract

Xenopus laevis, commonly known as the African clawed frog, is a useful model in developmental biology. The tail of the Xenopus tadpole completely regenerates by 7–14 days after amputation. This regeneration is similar to tissue renewal in mammals. A ‘‘refractory period’’ occurs during development during which tail regenerative ability is lost in tadpoles. Because of this refractory period, the Xenopus tadpole tail is an ideal model for studying changes in regenerative ability in mammals. Tail regeneration in Xenopus tadpoles requires bioelectrical signaling, which involves slow changes in ion content and resting membrane voltage. For optimal treatment to provide bioelectrical signals for successful regeneration, techniques need to be developed for precise temporal control of resting membrane voltage. In this article, the authors discuss a technique that assists with control of resting membrane voltage in vivo. They demonstrate that this method controls regenerative responses in the tadpole tail. The authors propose a new hypothesis for how ion content is converted into alterations in cell behavior and transcription. The authors hypothesize that the sodium/butyratre transporter SLC5A8 is a mechanism by which some systems may link epigenetic chromatin modifications with bioelectric events (changes in ion content). Determining the mechanisms by which ion flow modulates gene expression will likely provide further understanding on cell biology and evolution of morphogenetic pathways, and contribute to development of treatments that use bioelectricity. Mammalian tissue repair involves a complex, dynamic interplay among cells located at the site of injury and white blood cells recruited to the site. These interactions lead to various processes, including inflammation and tissue differentiation, necessary for repair. In contrast, limb regeneration in urodeles (e.g., salamanders and newts) involves a short period of inflammation, but this is followed by blastema formation that results in a new organ that is fully functional. The authors focus on limb regeneration in Xenopus laevis, which as well as being a useful embryological model, also plays an important role in developmental studies of the immune system and for investigation of regenerative mechanisms. They first review studies on gene expression in amputated Xenopus limbs at various developmental stages involving regeneration and non-regeneration. These studies show that inflammation and regenerative capacity are inversely correlated. The authors also review non-mammalian immune system features involved in the role of inflammation in the balance between regeneration and fibrosis. The authors show results testing the hypothesis that factors controlling the inflammatory response to injury affect regeneration. They compare the effects of antiinflammatory agents and a proinflammatory adjuvant. The data reviewed by the authors suggest that studies on ontogenic immunological changes that occur in Xenopus laevis are useful for determining how inflammation affects blastema formation. An important question is the extent to which differentiating blastema cells resemble mammalian mesenchymal stem cells. Many lizards have the remarkable ability of tail and spinal cord regeneration. Although tail regeneration in lizards has been well studied, further characterization of the anatomy of the regenerated tale is required. The authors examined the anatomy of the original and regenerated tail in the green anole Anolis carolinensis. They chose this species as a model because the process of tail shedding and regeneration is well understood, as well as the fact that the genome has been sequenced, making it a good model for understanding genetic regulation for tail regeneration. The authors investigated the musculature, chondrology, and osteology of the original and regenerated tail in A. carolinensis. The authors found differences in musculature between the original and regenerated tail, suggesting major functional differences between the two types of tails. Notably, the regenerated tail is thought to be less able to perform fine movements. The authors' findings of detailed anatomy of the tail in A. carolinensis could be useful for future genetic and developmental studies on tail regeneration in lizards, and potentially to regeneration in mammals. Ellen C. Jensen*