Scientists have discovered a gene shared by salamanders, mice, and zebrafish that could lead to new therapies for limb regeneration in humans, according to research published this week. Wake Forest Assistant Professor of Biology Josh Currie collaborated with colleagues from Duke University and the University of Wisconsin-Madison on the study released on Apr. 16.
The findings are significant because more than one million limb amputations occur globally each year due to vascular diseases like diabetes, traumatic injuries, cancer, or infections. As populations age and diabetes rates rise, the number of amputations is expected to increase. Researchers hope their work will eventually offer an alternative to prosthetics by restoring natural limb function.
Currie said the project brought together three labs studying different organisms: “This significant research brought together three labs, working across three organisms to compare regeneration,” he said. “It showed us that there are universal, unifying genetic programs that are driving regeneration in very different types of organisms, salamanders, zebrafish and mice.”
The team focused on SP genes—specifically SP6 and SP8—which they found were essential for limb regeneration in all three species studied. Using CRISPR gene-editing technology in his lab at Wake Forest University, Currie’s team removed SP8 from axolotl salamanders; as a result, these animals could not properly regenerate their limb bones. A similar effect was seen when mouse digits lacked both SP6 and SP8.
Building on these results, David A. Brown’s lab at Duke used a tissue regeneration enhancer from zebrafish to develop a viral gene therapy delivering FGF8—a molecule usually activated by SP8—to encourage digit bone regrowth in mice missing these genes.
Currie said this approach offers “proof of principle” for future therapies: “We can use this as a kind of proof of principle that we might be able to deliver therapies to substitute for this regenerative style of epidermis in regrowing tissue in humans.” He added that while more research is needed before moving from mouse digits to human limbs, the study lays foundational groundwork: “Scientists are pursuing many solutions for replacing limbs including bioengineered scaffolds and stem cell therapies,” Currie explained. “The gene-therapy approach in this study is a new avenue that can complement and potentially augment what will surely be a multi-disciplinary solution to one day regenerate human limbs.”
He also highlighted the importance of collaboration: “Many times scientists work in their silos: we’re just working in axolotl or we’re just working in mouse or just working in fish,” Currie said. “A real standout feature of this research is that we work across all these different organisms. That is really powerful and it’s something that I hope we’ll see more of in the field.”
Researchers say continued cross-species studies may further advance regenerative medicine.
