The axolotl seems like something out of science fiction. This perpetually youthful-looking Mexican salamander possesses a superpower that defies biology as we know it: the ability to regenerate entire limbs, parts of its heart, and even its spinal cord. But how does an amputated limb know whether to regenerate an entire arm from the shoulder down or just a hand from the wrist? This mystery of “positional identity” has fascinated scientists for decades. A team at Northeastern University, led by James Monaghan, has unraveled a key piece of this biological puzzle. In a study published in Nature Communications, the researchers reveal an elegant molecular mechanism that acts like a GPS coordinate system for regenerating cells. Surprisingly, the secret lies not in producing more of a chemical signal, but in how quickly it is destroyed. Monaghan’s lab houses about 500 axolotls cared for by a team ranging from undergraduate students to postdocs. “Raising axolotls involves managing a complex aquatic system and being patient, as they reach sexual maturity within a year. It’s slower than with other model organisms, but also more exciting. In many experiments, the team is exploring completely new terrain,” Monaghan says. For more than two decades, Monaghan’s lab has been studying the axolotl to understand how it regenerates complex organs such as its limbs, spinal cord, heart, and tail. His lab’s research focuses on uncovering why nerves are essential to this process and what unique cellular properties allow axolotls to regenerate tissues that other animals cannot. These findings could transform our understanding of bodily regeneration and have important applications in regenerative medicine. James Monaghan at work in the lab. Photograph: Alyssa Stone/Northeastern University “For years we’ve known that retinoic acid, a derivative of vitamin A, is a crucial molecule that screams to cells ‘build a shoulder!’” explains Monaghan. “But the puzzle was how the cells in the regenerating limb-stump controlled their levels so precisely to know exactly where they were on the axis from shoulder to hand.”