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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.


E&E News
09-06-2025
- Politics
- E&E News
Trump cuts would scrap USGS biological research arm
The Trump administration wants to unplug a high-powered U.S. Geological Survey research program whose scientists have helped protect wildlife, manage forests, thwart pests and illuminate nature for over three decades. Eliminating the biological research branch of the USGS, as called for in President Donald Trump's fiscal 2026 budget proposal, would accelerate the administration's targeting of scientific experts and studies already shown in layoffs and grant cancellations at the National Science Foundation and National Institutes of Health. But the potential scrapping of the USGS program is also goading some scientists out of their labs and into lobbying, as they deploy letters, phone calls, professional advocates, social media messaging, virtual rallies and more in their bid to save a nearly $300 million-a-year program. Advertisement 'It seems largely political,' Shahid Naeem, a prominent Columbia University professor of ecology, said of the proposed USGS budget slashing in an interview. 'And from a scientific point of view, it's really going to cost the country billions of dollars if we eliminate these programs which keep watch on things like avian influenza, water quality and forest fires.' Ron Pulliam, an emeritus professor at the University of Georgia, added in an email that elimination of the program is a 'terrible idea based on the assumption that if you are unaware of bad news everything will be OK.' More than 30 years ago, Pulliam was the first head of the biological research program that's now called the USGS Ecosystem Mission Area. The Ecosystem Mission Area is one of five designated mission areas within USGS. It received about $293 million for fiscal 2025. Trump's proposal would drop it to zero in fiscal 2026. The program includes 16 research centers, from the Great Lakes Science Center in Ann Arbor, Michigan, to the Western Fisheries Research Center in Seattle. Scientists in Colorado, for instance, have examined how wildland fire risks and the potential benefits of forest thinning can best be communicated to at-risk communities. Elsewhere, researchers monitor bat populations threatened by wind turbines and fungal disease. Still other USGS scientists are working to fight quagga mussels, a particularly vexing invasive species. In Alaska, they count loon populations and measure high-altitude snow packs. They keep an eye on sediment tainting Chesapeake Bay and on the Everglades' altered water flows. The program helps fund, as well, cooperative research units like one at Oregon State University, where more than 30 scientists, graduate students and assistants study fish and wildlife. 'Losing the EMA means losing many critical partners and projects that promote evidence-based recommendations for conservation of natural resources,' said Selina Heppell, professor and head of the university's Department of Fisheries, Wildlife and Conservation Sciences, in an email. Bipartisan appeal Last year, then-USGS Director David Applegate promoted a proposed 10 percent budget increase for the Ecosystem Mission Area by citing its work on 'migration science for huntable big-game populations.' The choice to highlight hunting benefits before a House panel stocked with hunting-friendly GOP members could be interpreted as tactical, with Applegate citing 'the unique USGS expertise and technical capacity' that helps sustain economies in the West that rely on hunting and tourism, as well as those where people hunt for subsistence. Applegate is now back in a career position as USGS's chief scientist. The agency currently has an acting director while Trump's nominee — geologist Ned Mamula — awaits Senate confirmation. The Trump administration's proposed fiscal 2026 budget does not elaborate on the proposal to end the Ecosystem Mission Area's funding. The proposed budget reports that the USGS employed about 7,870 full-time workers in fiscal 2024. The proposed budget envisions total USGS employment falling to 5,153 in fiscal 2026. In a budget summary, the USGS cites its intention to eliminate 'grants to universities and other work that is duplicative of non-Federal research programs' and that 'supports social agendas [like] climate change research.' The agency cites plans to focus instead on 'higher priority energy and minerals activities' and to help 'streamline government.' In response to a request from POLITICO's E&E News for additional details about personnel numbers, future work and the rationale for eliminating the program, the Interior Department provided a statement. 'Interior proudly supports President Trump's 'One Big Beautiful Bill' — a historic, America First budget that delivers middle-class tax cuts, unleashes American energy, secures our borders, and invests in the infrastructure and security of our public lands,' the statement said. The genesis of the proposal is unclear, but the notion cropped up in the Heritage Foundation's Project 2025 policy playbook. The chapter on the Interior Department was authored by conservative attorney William Perry Pendley, who served as de facto acting director of the Bureau of Land Management in Trump's first term. 'Abolish the Biological Resources Division of the U.S. Geological Survey and obtain necessary scientific research about species of concern from universities via competitive requests for proposals,' the Project 2025 Interior Department chapter stated. The 'Biological Resources Division' was formerly the name of what has been called the Ecosystem Mission Area for the last 15 years. The Project 2025 playbook did not elaborate on the perceived benefits of ending the USGS ecosystem work. Reached by telephone Wednesday, Pendley said, 'I'm not going to discuss that right now. I appreciate the call.' Scientists lobby Supporters of the USGS research are trying to call attention to the proposed cuts. The National Wildlife Federation on May 22 convened a 'virtual rally' that drew about 2,000 participants to an hour-long program in support of the USGS Ecosystem Mission Area. Naeem, a former president of the 8,000-member Ecological Society of America, ventured onto Capitol Hill in May to discuss the proposal with Democratic congressional offices. 'We've been in constant communication with our members to be proactive,' Naeem said. 'If our people speak up all across the United States and talk to their senators and members of Congress, that's probably where we're going to have the most effect.' Upwards of 60 science-related organizations, from the American Geophysical Union to the Weed Science Society of America, signed an April 30 letter to Interior Secretary Doug Burgum and a May 9 letter to leaders of the House and Senate appropriations committees and both congressional natural resources committees. An umbrella group called the USGS Coalition, representing more than 85 academic, business and scientific organizations, has likewise weighed in with testimony presented in April to House appropriators. The director of one cooperative state-and-federal research center, granted anonymity because they had not been authorized to speak publicly about the issue, said, 'We are calling our representatives, signing letters and writing editorials for newspapers.' For the lawmakers, the proposed USGS budget cut is just one of many they will face. Asked on Thursday if he had any thoughts about the proposal, Republican Rep. Mike Simpson of Idaho, the chair of the House Interior and Environment Appropriations Subcommittee, said simply 'no.' A spokesperson for the conservative Pacific Legal Foundation likewise said the organization had no reaction at the proposal at the present time. The program's roots stretch back to 1993, when the Clinton administration merged Interior's scattered biological research work from seven bureaus into a new National Biological Service contained within the department. It was not always a smooth transition, facing both bureaucratic and political resistance. Conservative lawmakers, in particular, cited alleged threats to private property rights from what had initially been dubbed the National Biological Survey. 'There was a perception that it was a band of environmental activists who would seek to find endangered species on private property, and I would say, in some instances, that probably happened,' then-Rep. Wayne Gilchrest, a moderate Maryland Republican, said in 1995. In 1996, the National Biological Service was again renamed and transferred into the USGS. In 2010, as part of a larger USGS reorganization. Most of this work was folded into the newly established Ecosystem Mission Area. Other USGS mission areas, such as Natural Hazards and Water Resources, would get less money but still survive under Trump's proposed fiscal 2026 budget. Reporter Garrett Downs also contributed.


New York Times
31-05-2025
- Business
- New York Times
Trump's Proposed Budget Would Cut a Major Ecology Program
The Trump administration's proposed budget for 2026 slashes about 90 percent of the funding for one of the country's cornerstone biological and ecological research programs. Known as the Ecosystems Mission Area, the program is part of the U.S. Geological Survey and studies nearly every aspect of the ecology and biology of natural and human-altered landscapes and waters around the country. The 2026 proposed budget allocates $29 million for the project, a cut from its current funding level of $293 million. The budget proposal also reduces funds for other programs in the U.S. Geological Survey, as well as other federal science agencies. The budget still needs to be approved by Congress and scientists are seizing the opportunity to save the E.M.A. In early May, more than 70 scientific societies and universities signed a letter to Interior Secretary Doug Burgum, urging him not to eliminate the program. Abolishing the E.M.A. was an explicit goal of Project 2025, the blueprint for shrinking the federal government produced by the conservative Heritage Foundation. That work cited decades-long struggles over the Interior Department's land management in the West, where protections for endangered species have at times prevented development, drilling and mining. Want all of The Times? Subscribe.


Russia Today
06-05-2025
- Health
- Russia Today
Trump ends virus research funding
US President Donald Trump has issued an executive order restricting federal funding for 'gain-of-function' research into viruses and other biological agents in the US and abroad, including China. 'Gain-of-function' or 'dual use' studies have been gaining controversy after the COVID-19 pandemic. Trump has suggested that a lab leak in Wuhan, China, where US-funded research was based, was the source of the outbreak that brought the world to a standstill. Beijing has denied the claims and accused Washington of trying to smear China. Unrestricted gain-of-function research could 'significantly endanger the lives of American citizens,' among other things, Trump's order alleges, and lead to 'widespread mortality, an impaired public health system, disrupted American livelihoods, and diminished economic and national security.' Trump ordered an end to federal funding for 'dangerous gain-of-function research' in 'countries of concern,' such as China and Iran, citing 'biological threats' . He argued that US taxpayer-funded research should help Americans, without threatening national security. Similar US-based programs will be suspended for at least 120 days during which existing policies on dual-use research will be revised or replaced, according to the document. The document also blamed the administration of Trump's predecessor Joe Biden for allowing 'dangerous' research into viruses in the US and 'actively' approving funding for similar projects abroad, where Washington's oversight is limited. Moscow has repeatedly alleged that US-backed biological research laboratories in Ukraine and other countries near Russian borders are involved in bioweapons research. Washington has acknowledged providing support to laboratories in Ukraine but insisted that they were owned by Kiev and focused solely on preventing the outbreaks of infectious diseases and developing vaccines. The Defense Ministry in Moscow has claimed that the US has transferred unfinished Ukrainian projects to post-Soviet states and Southeast Asia, while also singling out Africa as a focal point of Washington's interests.


Gizmodo
06-05-2025
- Health
- Gizmodo
Trump Signs Executive Order to Limit Funding for Controversial Gain-of-Function Research
President Donald Trump signed an executive order Monday that seeks to limit federal funding for gain-of-function research, which is used to study how pathogens can become more harmful by causing mutations in the lab. The EO was signed by the president in the Oval Office of the White House, with HHS Secretary Robert F. Kennedy Jr. and other top health officials by Trump's side, who all tried to suggest the covid-19 pandemic originated from a leak at a research facility in China that was conducting gain-of-function research. They falsely claimed the so-called lab leak theory was the consensus view among scientists. Titled 'Improving the Safety and Security of Biological Research,' the executive order directs the White House's Director of the Office of Science and Technology Policy to work with federal agencies to issue guidance that will end federal funding of all gain-of-function research in the U.S. and abroad. The order also directs agencies to track gain-of-function research in the U.S. that isn't federally funded and figure out how to stop it. Gain-of-function research has trade-offs and has long been debated in the scientific community. The journal Nature published a study about how to create a mutant form of a bird flu in 2012 that was criticized at the time. And that feels especially relevant to those of us living through the current H5N1 outbreak that's jumped to cows and isn't yet transmissible from human to human. But most of the debate around gain-of-function research has nothing to do with disclosing methods in scientific journals. The research is conducted to create a kind of 'pre-emptive strike' against potentially dangerous viruses to learn how they work, as Gizmodo explained in 2014. And while they have risks, they also have benefits. Being able to figure out how viruses could mutate allows for an early understanding of how to fight them with vaccines. 'Just about every mutation scientists can make, nature has already made,' Patrick Moore, virologist at the University of Pittsburgh, told Gizmodo in 2017. 'That's something we should be aware of, and that's why we have new viruses cropping up all the time.' But the risks are very real. President Barack Obama halted funding for GOF research in 2014 after several security lapses involving lethal bugs, including anthrax at the CDC, smallpox at the FDA, and bird flu at the USDA. The NIH lifted a ban on gain-of-function research in late 2017 during President Trump's first term. While there's real reasonable debate about the role of gain-of-function research and its safety, the press event at the White House on Monday included a lot of highly contested claims that are more the realm of conspiracy theorists than serious-minded health officials. FDA commissioner Marty Makary, who was standing near Trump and Secretary Kennedy to talk with reporters as the president signed the EO, pushed a definitive narrative about the origins of covid-19 that is still very controversial. 'It's unbelievable to think the entire nightmare of covid was likely preventable, and you had good instincts early on, Mr. President, in suggesting it came from the Wuhan lab,' Makary told Trump. 'That is now the leading theory among scientists.' The most recent studies on the lab leak theory, looking at genomic data, still suggest natural origins. Back in February, one study found that most virologists and other scientists with relevant expertise still don't think the lab leak theory is the best explanation for how covid-19 came into the world. But that doesn't fit with the tight narrative that Trump and his people want to believe. It's entirely possible that covid-19 was caused by a lab leak. We just don't have the solid data to support that idea and anyone using that as a rationale for banning gain-of-function research is probably trying to sell you on a worldview that relies less on science and more on ideology.