Wake Forest Scientists Identify Shared Genetic Blueprint for Limb Regeneration Across Axolotls, Fish, and Mice

Wake Forest researchers identify universal SP genes in axolotls and mice that could lead to revolutionary gene therapies for regrowing human limbs.

By: AXL Media

Published: Apr 17, 2026, 7:37 AM EDT

Source: Information for this report was sourced from Wake Forest University

A Universal Program for Biological Regrowth

A collaborative effort between biologists and surgeons has uncovered a unifying genetic mechanism that governs the regeneration of complex limbs. By comparing the regenerative processes in axolotls, zebrafish, and mice, researchers led by Wake Forest Assistant Professor Josh Currie identified that "SP genes" are vital for rebuilding bone and tissue. The study suggests that while humans have lost the natural capacity to regrow entire limbs, the underlying genetic architecture for such a process is conserved across species. This discovery offers a foundational roadmap for developing gene therapies that could one day address the needs of more than 1 million people who undergo amputations annually.

The Selection of Model Organisms

The research team chose three distinct species to understand the limits and possibilities of regeneration. The axolotl was included for its unparalleled ability to regrow complete limbs and organs, while the zebrafish provided a model for rapid appendage regrowth through its tail fins. Mice were selected to represent mammalian biology, specifically because they retain a limited ability to regenerate the tips of their digits. According to Professor Currie, observing the same SP6 and SP8 genes at work in the epidermis of all three species confirmed that these genetic programs are universal rather than unique to salamanders.

CRISPR Technology and Genetic Dependency

To verify the role of these specific genes, the researchers utilized CRISPR gene-editing technology to remove SP8 from the axolotl genome. Without this gene, the salamanders were unable to properly regenerate limb bones, a finding that was mirrored in mice missing both SP6 and SP8. This experimentation demonstrated that the SP genes act as essential "on switches" for the biological pathways required for skeletal reconstruction. The identification of this dependency is a critical step in isolating the specific molecular signals that human skin fails to produce following a traumatic injury.