Latest news with #JamesMonaghan
Yahoo
22-06-2025
- Health
- Yahoo
Axolotl Discovery Brings Us Closer Than Ever to Regrowing Human Limbs
Axolotls (Ambystoma mexicanum) have the incredible ability to regenerate limbs, and even entire organs. And of course, people want to know how we might get our own human bodies to do it, too. A team of biologists from Northeastern University and the University of Kentucky has found one of the key molecules involved in axolotl regeneration. It's a crucial component in ensuring the body grows back the right parts in the right spot: for instance, growing a hand, from the wrist. "The cells can interpret this cue to say, 'I'm at the elbow, and then I'm going to grow back the hand' or 'I'm at the shoulder… so I'm going to then enable those cells to grow back the entire limb'," biologist James Monaghan explains. That molecule, retinoic acid, is arranged through the axolotl body in a gradient, signaling to regenerative cells how far down the limb has been severed. Closer to the shoulder, axolotls have higher levels of retinoic acid, and lower levels of the enzyme that breaks it down. This ratio changes the further the limb extends from the body. The team found this balance between retinoic acid and the enzyme that breaks it down plays a crucial role in 'programming' the cluster of regenerative cells that form at an injury site. When they added surplus retinoic acid to the hand of an axolotl in the process of regenerating, it grew an entire arm instead. In theory, the human body has the right molecules and cells to do this too, but our cells respond to the signals very differently, instead forming collagen-based scars at injury sites. Next, Monaghan is keen to find out what's going on inside cells – the axolotl's, and our own – when those retinoic acid signals are received. "If we can find ways of making our fibroblasts listen to these regenerative cues, then they'll do the rest. They know how to make a limb already because, just like the salamander, they made it during development," Monaghan says. "It could help with scar-free wound healing but also something even more ambitious, like growing back an entire finger," he adds. "It's not out of the realm [of possibility] to think that something larger could grow back like a hand." The research is published in Nature Communications. Stomach Ulcer Bacteria Could Be a Surprise Ally Against Alzheimer's Early Signs of Cancer Found in Patient Blood 3 Years Before Diagnosis Fecal Transplants Present a Concerning Risk For Some, Study Finds
WIRED
17-06-2025
- Science
- WIRED
Scientists Discover the Key to Axolotls' Ability to Regenerate Limbs
Jun 17, 2025 5:00 AM A new study reveals the key lies not in the production of a regrowth molecule, but in that molecule's controlled destruction. The discovery could inspire future regenerative medicine. Axolotls in Professor James Monaghan's laboratory. Photograph: Alyssa Stone/Northeastern University 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.' To unpick this mystery, the team focused on a cluster of stem cells that form at the wound site after a limb is lost in animals like the axolotl that are capable of regeneration. Known as the blastema, it's this base of stem cells that then orchestrates regeneration. The prevailing theory was that differences in retinoic acid production might explain why a shoulder (proximal) amputation leads to an entire limb being regenerated, while a wrist (distal) amputation only regenerates the hand. 'Our big surprise was to discover that the key was not in how much retinoic acid was produced, but in how it was degraded,' says Monaghan. The team discovered that cells in the distal part of the limb, the wrist, are awash in an enzyme called CYP26B1, whose sole function is to destroy retinoic acid. In contrast, cells in the shoulder have hardly any of this enzyme, allowing retinoic acid to accumulate to high levels. This difference creates a chemical gradient along the limb: lots of retinoic acid in the shoulder, little in the wrist. It is this gradient that informs cells of their exact location. In humans, this pathway of cellular plasticity is absent or closed. 'Therefore, the great challenge is to understand how to induce this blastemal state in our cells, a key transient structure in regeneration. If achieved, it would be possible for our cells to respond again to positional and regenerative signals, as they do in the axolotl,' explains the researcher. Tricking the Cells Into Over-Regenerating To confirm their discovery, the researchers conducted an experiment. They amputated axolotl legs at the wrist and administered a drug called talarozole, which inhibits the CYP26B1 enzyme. By 'turning off the brakes,' retinoic acid accumulated to extremely high levels in a place where it normally shouldn't. As a result the wrist cells, 'confused' by the high concentration of retinoic acid, interpreted position as being the shoulder. Instead of regenerating a hand, they proceeded to regenerate a complete, duplicated limb. 'It was the ultimate test,' Monaghan says. Different limb regenerations of axolotls treated with talarozole. Photograph: Alyssa Stone/Northeastern University The team went a step further to identify which genes were activated by these high levels of retinoic acid. They discovered a master gene that was specifically activated in shoulder areas: Shox . An abbreviation of 'short stature homeobox gene,' Shox is so called because mutations to it in humans cause short stature. 'We identified Shox as a critical instruction manual in this process,' Monaghan explains. 'It's the gene that tells developing cells to 'build the arm and forearm bones.'' To confirm this, the team used Crispr gene-editing technology to knock out the Shox gene in axolotl embryos. The resulting animals had peculiar limbs: normal-sized hands and fingers, but significantly shorter and underdeveloped arms and forearms. This demonstrated that Shox is essential for shaping proximal, but not distal, structures, revealing that regeneration uses distinct genetic programs for each limb segment. This study not only solves a long-standing mystery of regenerative biology, but also provides a molecular road map. By understanding how the axolotl reads and executes its genetic instructions for regeneration, scientists can begin to think about how, someday, we might learn to write our own genetic instructions. An axolotl. Photograph: Alyssa Stone/Northeastern University 'The axolotl has cellular properties that we want to understand at the deepest level,' says Monaghan. 'While regeneration of a complete human limb is still in the realm of science fiction, each time we discover a piece of this genetic blueprint, such as the role of CYP26B1 and Shox , we move one step closer to understanding how to orchestrate complex tissue repair in humans.' To bring this science closer to clinical applications, one crucial step is to succeed in inducing blastema formations of stem cells at sites of amputation in humans. 'This is the 'holy grail' of regenerative biology. Understanding the minimal components that make it up—the molecular signals, the cellular environment, the physiological conditions—would allow us to transform a scar into a regenerative tissue,' explains Monaghan. In his current research, there are still gaps to be filled: how the CYP26B1 gradient is regulated, how retinoic acid connects to the Shox gene, and what downstream factors determine the formation of specific structures, such as the humerus or radius bones. From Healing to Regeneration Monaghan explains that axolotls do not possess a 'magic gene' for regeneration, but share the same fundamental genes as humans. 'The key difference lies in the accessibility of those genes. While an injury in humans activates genes that induce scarring, in salamanders there is cell de-differentiation : the cells return to an embryonic-like state, where they can respond to signals such as retinoic acid. This ability to return to a 'developmental state' is the basis of their regeneration,' explains the researcher. So, if humans have the same genes, why can't we regenerate? 'The difference is that the salamander can reaccess that [developmental] program after injury.' Humans cannot—they only access this development pathway during initial growth before birth. 'We've had selective pressure to shut down and heal,' Monaghan says. 'My dream, and the community's dream, is to understand how to make the transition from scar to blastema.' James Monaghan. Photograph: Alyssa Stone/Northeastern University Monaghan says that, in theory, it would not be necessary to modify human DNA to induce regeneration, but to intervene at the right time and place in the body with regulatory molecules. For example, the molecular pathways that signal a cell to be located in the elbow on the pinky side—and not the thumb—could be reactivated in a regenerative environment using technologies such as Crispr. 'This understanding could be applied in stem cell therapies. Currently, laboratory-grown stem cells do not know 'where they are' when they are transplanted. If they can be programmed with precise positional signals, they could integrate properly into damaged tissues and contribute to structural regeneration, such as forming a complete humerus,' says the researcher. After years of work, understanding the role of retinoic acid—studied since 1981—is a source of deep satisfaction for Monaghan. The scientist imagines a future where a patch placed on a wound can reactivate developmental programs in human cells, emulating the regenerative mechanism of the salamander. Although not immediate, he believes that cell engineering to induce regeneration is a goal already within the reach of science. He reflects on how the axolotl has had a second scientific life. 'It was a dominant model a hundred years ago, then fell into disuse for decades, and has now reemerged thanks to modern tools such as gene editing and cell analysis. The team can study any gene and cell during the regenerative process. In addition, the axolotl has become a cultural icon of tenderness and rarity.' This story originally appeared on WIRED en Español and has been translated from Spanish.
Miami Herald
12-06-2025
- Health
- Miami Herald
Scientists studying axolotls in hopes of learning how to regrow limbs
With their goofy grins and feathery gills, axolotls have become stars of the pet world and video games like Minecraft. But these small, smiling salamanders are also helping scientists explore a medical mystery: Can people someday regrow arms or legs? Axolotls are special because they can regrow body parts no matter the age. Lose a leg? They'll grow it back. Damage to their heart, lungs or even brain? They can also repair that! 'This species is special,' lead researcher James Monaghan, a biologist at Northeastern University in Boston, told The Washington Post. They have 'really become the champion of some extreme abilities that animals have.' In a new study -- published Tuesday in Nature Communications -- Monaghan's team used genetically engineered axolotls that glow in the dark to learn how this amazing process works. One mystery in limb regrowth is how cells 'know' which part of the limb to rebuild. If an axolotl loses its upper arm, it grows back the entire arm. But if the injury is farther down, only the lower arm and hand regrow. 'Salamanders have been famous for their ability to regenerate arms for centuries,' Monaghan said. 'One of the outstanding questions that has really plagued the field is how a salamander knows what to grow back.' The answer may be a small molecule called retinoic acid. It's related to vitamin A and often used in skin-care products under the name retinol. The molecule acts like a GPS, helping cells know where they are on the body and what part to rebuild. Monaghan's team worked with axolotls that were genetically engineered to glow when retinoic acid was active. Then, they amputated limbs -- after giving the animals anesthesia -- and tracked their health, The Post reported. Monaghan said researchers monitored their health closely. 'They don't show signs of pain or distress after limb amputation the way mammals might, and they regenerate fully within weeks,' he said. When axolotls were given a drug that blocked the breakdown of retinoic acid, their limbs didn't regrow right -- an upper arm would form where a lower arm should be. Axolotls not given the drug regrew their limbs normally. This suggests that retinoic acid tells cells where they are and what part to grow. Higher levels of the acid seem to signal a spot closer to the body's center, according to The Post. 'While we are still far from regenerating human limbs, this study is a step in that direction,' said Prayag Murawala, a researcher at MDI Biological Laboratory in Maine, who helped make the glowing axolotls used in the study. Monaghan thinks this could help humans someday. 'We all have the same genes,' he said. 'We've all made these limbs when we were embryos.' The challenge is figuring out how to turn those same genetic blueprints back on later in life -- something axolotls can do but humans can't yet. 'It's one of the oldest questions in biology, but it's also the most futuristic-looking,' he said. Thanks to a growing interest in axolotls, especially among kids, this unique animal is helping to drive cutting-edge science. 'It's a little surreal,' Monaghan added. 'You just see axolotls at the airport, axolotls at the mall. My kids are coming home with axolotl toys all the time, because people know what I do.' More information The San Diego Zoo has more on axolotls. Copyright © 2025 HealthDay. All rights reserved. Copyright 2025 UPI News Corporation. All Rights Reserved.
Yahoo
12-06-2025
- Health
- Yahoo
Axolotls' Regenerative Abilities Could Teach Scientists a Thing or Two About Medicine
Axolotls might be cute enough to feature in a wide variety of games, TV shows, and children's toy brands, but that's not all that makes them special: The species is also exceptionally good at regenerating lost limbs and organs. Thinking that these smiling salamanders might have something to teach modern medicine, researchers in Boston are unpacking the molecules responsible for axolotls' rapid regrowth. One molecule in particular could someday help heal human wounds and replace lost limbs. The molecule is retinoic acid, according to a paper published Tuesday in Nature Communications. Human bodies make retinoic acid out of vitamin A (obtained by eating fish, dairy, and vegetables) and occasionally receive it through cosmetic retinoids, which are used to treat acne. The molecule is key to cell growth, and if too much of it is absorbed during pregnancy, it can lead to serious birth defects. In axolotls, retinoic acid takes that role a step further. Biologists at Northeastern University have found that axolotls rely on a retinoic acid signaling gradient, which allows different concentrations of the molecule to work in various parts of the body. Their shoulders, for instance, contain more retinoic acid (and less of the enzyme CYP26B1, which breaks it down) than their palms. When an axolotl loses its arm, the retinoic acid in its shoulder tells its fibroblasts, or regenerative cells, how to build a new one. This axolotl is regenerating an arm after an attack. Credit: HTO/Wikimedia Commons (public domain) According to Northeastern's write-up, this discovery led the researchers to conduct experiments that were, in their words, "pretty Frankensteiny." Adding bonus retinoic acid to an axolotl's hand allowed it to grow a duplicate limb, for example. But simply injecting a human with extra retinoic acid won't allow them to generate new body parts. Now, the researchers are working to untangle "shox," short for the "short homeobox gene." This gene activates whenever retinoic acid signaling increases in an axolotl's body, suggesting that shox plays a part in limb regeneration. Indeed, removing shox from an axolotl's genome caused it to grow "very short arms," albeit with normal-sized hands. Understanding how retinoic acid and shox collaborate will be the next step toward wielding axolotl insights in human medicine. "If we can find ways of making our fibroblasts listen to these regenerative cues, then they'll do the rest," said biologist and study co-author James Monaghan. "They know how to make a limb already because, just like the salamander, they made it during development."
Yahoo
11-06-2025
- Health
- Yahoo
Scientists studying axolotls in hopes of learning how to regrow limbs
With their goofy grins and feathery gills, axolotls have become stars of the pet world and video games like Minecraft. But these small, smiling salamanders are also helping scientists explore a medical mystery: Can people someday regrow arms or legs? Axolotls are special because they can regrow body parts no matter the age. Lose a leg? They'll grow it back. Damage to their heart, lungs or even brain? They can also repair that! "This species is special," lead researcher James Monaghan, a biologist at Northeastern University in Boston, told The Washington Post. They have "really become the champion of some extreme abilities that animals have." In a new study -- published Tuesday in Nature Communications -- Monaghan's team used genetically engineered axolotls that glow in the dark to learn how this amazing process works. One mystery in limb regrowth is how cells "know" which part of the limb to rebuild. If an axolotl loses its upper arm, it grows back the entire arm. But if the injury is farther down, only the lower arm and hand regrow. "Salamanders have been famous for their ability to regenerate arms for centuries," Monaghan said. "One of the outstanding questions that has really plagued the field is how a salamander knows what to grow back." The answer may be a small molecule called retinoic acid. It's related to vitamin A and often used in skin-care products under the name retinol. The molecule acts like a GPS, helping cells know where they are on the body and what part to rebuild. Monaghan's team worked with axolotls that were genetically engineered to glow when retinoic acid was active. Then, they amputated limbs -- after giving the animals anesthesia -- and tracked their health, The Post reported. Monaghan said researchers monitored their health closely. "They don't show signs of pain or distress after limb amputation the way mammals might, and they regenerate fully within weeks," he said. When axolotls were given a drug that blocked the breakdown of retinoic acid, their limbs didn't regrow right -- an upper arm would form where a lower arm should be. Axolotls not given the drug regrew their limbs normally. This suggests that retinoic acid tells cells where they are and what part to grow. Higher levels of the acid seem to signal a spot closer to the body's center, according to The Post. "While we are still far from regenerating human limbs, this study is a step in that direction," said Prayag Murawala, a researcher at MDI Biological Laboratory in Maine, who helped make the glowing axolotls used in the study. Monaghan thinks this could help humans someday. "We all have the same genes," he said. "We've all made these limbs when we were embryos." The challenge is figuring out how to turn those same genetic blueprints back on later in life -- something axolotls can do but humans can't yet. "It's one of the oldest questions in biology, but it's also the most futuristic-looking," he said. Thanks to a growing interest in axolotls, especially among kids, this unique animal is helping to drive cutting-edge science. "It's a little surreal," Monaghan added. "You just see axolotls at the airport, axolotls at the mall. My kids are coming home with axolotl toys all the time, because people know what I do." More information The San Diego Zoo has more on axolotls. Copyright © 2025 HealthDay. All rights reserved.
