Researchers comparing appendage regrowth in salamanders, fish and mice report that two related genes, SP6 and SP8, are activated in regenerating skin tissue across species and are required for normal bone regrowth in animal models—findings they say could inform future regenerative-medicine strategies.
Scientists studying axolotls, zebrafish and mice have identified a conserved genetic program that appears to support appendage regrowth across these species, according to a report from Wake Forest University describing work published in the Proceedings of the National Academy of Sciences.
The team focused on two members of the SP family of transcription-factor genes—SP6 and SP8—which the researchers found were activated in the regenerating epidermis (skin tissue) in all three animal models. In gene-editing experiments, removing SP8 from axolotls using CRISPR prevented proper regeneration of limb bones, and mice missing SP6 and SP8 showed similar regeneration problems in injured digit tips.
Building on those results, researchers designed a viral gene-therapy approach using a zebrafish-derived “tissue regeneration enhancer” element to drive localized expression of FGF8, a signaling molecule described as normally activated by SP8. In mice, the treatment promoted bone regrowth in damaged digits and partially restored regeneration in animals lacking the SP genes.
The researchers emphasized that humans do not naturally regenerate limbs the way salamanders do, and that the work is early-stage. Still, they framed the cross-species genetic similarities and the mouse experiments as a step toward therapies that could eventually complement other approaches such as scaffolds and stem-cell strategies.
