Several animals are known to regenerate body parts. Zebrafish, for example, can regrow fins. Newts can regrow tails and even limbs. These organisms, however, may have few tissue-regeneration lessons that could help humans learn how to regain lost body parts. Zebrafish and newts appear to rely on repair mechanisms that are poorly conserved across species, and so they may be poor models of regeneration. But what about lizards?

Lizards can regenerate their tails. Moreover, as amniote vertebrates, lizards are evolutionarily more closely related to humans than other models of regeneration.

These facts encouraged researchers at Arizona State University to study the regenerating tail of the green anole lizard (Anolis carolinensis). In particular, these researchers, led by Kenro Kusumi, Ph.D., used next-generation molecular and computer analysis tools to examine the genes turned on in tail regeneration.

The researchers described their work August 20 in PLOS ONE, in an article entitled, “Transcriptomic Analysis of Tail Regeneration in the Lizard Anolis carolinensis Reveals Activation of Conserved Vertebrate Developmental and Repair Mechanisms.”

Dr. Kusumi and colleagues reported that their transcriptomic analysis revealed 326 genes in specific regions of the regenerating tail. These genes appear to activate multiple developmental and repair mechanisms.

“Specifically, genes involved in wound response, hormonal regulation, musculoskeletal development, and the Wnt and MAPK/FGF pathways were differentially expressed along the regenerating tail axis,” wrote the authors. “Furthermore, we identified two microRNA precursor families, 22 unclassified noncoding RNAs, and three novel protein-coding genes significantly enriched in the regenerating tail.”

The researchers also observed that the process of tail regeneration in the lizard does not match the dedifferentiation and blastema-based model as described in the salamander and zebrafish. Instead, the lizard’s regeneration process matches a model involving tissue-specific regeneration through stem/progenitor populations.

“We have identified one type of cell that is important for tissue regeneration,” said study co-author Jeanne Wilson-Rawls, Ph.D. “Just like in mice and humans, lizards have satellite cells that can grow and develop into skeletal muscle and other tissues.”

Regeneration, the authors noted, requires a cellular source for tissue growth. One potential source consists of satellite cells, which have been studied extensively for their involvement in muscle growth and regeneration in mammals and other vertebrates. These cells could contribute to the regeneration of skeletal muscle, and potentially other tissues, in the lizard tail.

Mammalian satellite cells in vivo are limited to muscle, the authors continued, but in vitro, with the addition of exogenous BMPs, they can be induced to differentiate into cartilage as well: “High expression levels of BMP genes in lizard satellite cells could be associated with greater differentiation potential, and further studies will help to uncover the plasticity of this progenitor cell type.”

“The pattern of cell proliferation and tissue formation in the lizard identifies a uniquely amniote vertebrate combination of multiple developmental and repair mechanisms,” the authors concluded. “We anticipate that the conserved genetic mechanisms observed in regeneration of the lizard tail may have particular relevance for development of regenerative medical approaches.”

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