Mice Heal Themselves in Response to a Common Signaling Molecule

A newly discovered way to induce scarless healing in mice depends on a highly conserved signaling pathway that is also present in humans.

Black and white portrait of Ida Emilie Steinmark, PhD
| 5 min read
A fluorescence microscopy image of a common mouse ear with a black background, an embedded bead visible as a white circle, and regenerating tissue around it shown in green.

The researchers at the University of Kentucky and the Hubrecht Institute embedded beads soaked in ERK-activation growth factor mix (shown in white in this fluorescence microscopy image of a mouse ear) into the ears of common mice, and the tissue regenerated in response (shown in green).

Antonio Tomasso

Register for free to listen to this article
Listen with Speechify
0:00
5:00
Share

The seemingly magical regrowth of salamander tails and starfish arms after injury has always captured the attention of scientists. In recent years, they have also been excited about the spiny mouse, a small rodent discovered in 2012 to shed and regrow its skin1 because the existence of a regenerating mammal hints at the possibility of scarless healing in mammals more broadly.

Now, researchers at the University of Kentucky and the Hubrecht Institute have shown that boosting the activation of extracellular signal-regulated kinase (ERK), a common signaling molecule, can help common mice heal themselves in the same way as spiny mice do,2 suggesting that the ability to regenerate could lie dormant in other mammals, including humans.

The regenerative capacity in mammals is still there.

—Monica Sousa, University of Porto

The team suspected that ERK was important for the spiny mouse’s self-healing because ERK plays an important role in tissue healing. They began by exploring whether injury-related activation of ERK naturally differed between spiny mice and common mice. To do this, they punched holes in the ears of both types of mice and measured the levels of phosphorylated (activated) ERK over the following days and weeks, as the common mouse ears became edged in scar tissue and the spiny mouse ears seamlessly closed.

“What we discovered was that ERK is equally activated at the onset of injury in both species, although activated to a higher degree [in spiny mice],” said biologist Ashley Seifert from the University of Kentucky, who led the work and first discovered the spiny mouse’s special abilities. That high ERK activation persisted in the spiny mouse ear for several weeks, whereas ERK activation in common mice dropped significantly after day 10.

To test if this prolonged high ERK activity was necessary for the spiny mouse’s scarless healing, the team used a chemical to inhibit the activating ERK phosphorylation. “It completely blocked regeneration,” Seifert said. In fact, when ERK activation was disrupted, the tissue switched to the scar-producing phenotype seen in the common mice.

Remarkably, it worked the other way, too. When Seifert’s team stimulated ERK activity to a higher level in common mice, either through embedded beads soaked in an ERK-boosting growth factor mix or through viral transduction of an ERK activator, their ear holes started growing back together seamlessly. Holes of two millimeters in radius closed completely, and while the boost was not quite enough to fully close larger holes of four millimeters, the ear tissue was clearly regenerating. “Maybe with a secondary infection, we would have seen more persistent activation,” he said.

Science will discover the ability to stimulate generation of tissues and organs where it does not normally occur.

—Ashley Seifert, University of Kentucky

Mónica Sousa, a neuroscientist at the University of Porto who was not involved with the study, said that the paper suggests that most mammals have the potential for regeneration. “The regenerative capacity in mammals is still there,” she said. “It’s probably dormant and has been evolutionarily pushed back.” She also suspects that there are mammals in the wild today with regenerative abilities that scientists have yet to discover.

Sousa’s own work shows how spiny mice don’t just grow back ear tissue but can regain motor function after suffering a spinal cord injury that would be devastating to other species.4 In that context, ERK has not shown up as a key player, but she plans to explore it. “The way in which it seems to be a master regulator, at least in this type of tissue, is really fascinating,” she said.

The fact that regeneration can be so easily induced in common mice raises the question of why most mammals, including humans, don’t normally have regenerative abilities. “It could be a protective mechanism for mammals to protect the cells from developing into tumors,” said coauthor Antonio Tomasso from the Hubrecht Institute. However, the team saw no indication that the high level of activated ERK led to cancer during the time of the experiment. “You also need other factors that stimulate cells to become cancer cells,” he said.

“Science will discover the ability to stimulate generation of tissues and organs where it does not normally occur,” said Seifert. “I now unabashedly think that [spiny mice] are probably one of our best current models for discovering how to translate some of what we know about regeneration into humans.”

Keywords

Meet the Author

  • Black and white portrait of Ida Emilie Steinmark, PhD

    Ida Emilie Steinmark, PhD

    Emilie is an assistant editor at the Scientist. She has a background in chemistry and biophysics, and she has previously written for the Guardian, Scientific American and STAT, among others.

Published In

<em>The Scientist </em>Fall 2023 cover
Fall 2023

Defying Dogma

To understand how memories are formed and maintained, neuroscientists travel far beyond the cell body in search of answers.

Share
You might also be interested in...
Loading Next Article...
You might also be interested in...
Loading Next Article...
3D illustration of a gold lipid nanoparticle with pink nucleic acid inside of it. Purple and teal spikes stick out from the lipid bilayer representing polyethylene glycol.
February 2025, Issue 1

A Nanoparticle Delivery System for Gene Therapy

A reimagined lipid vehicle for nucleic acids could overcome the limitations of current vectors.

View this Issue
Considerations for Cell-Based Assays in Immuno-Oncology Research

Considerations for Cell-Based Assays in Immuno-Oncology Research

Lonza
An illustration of animal and tree silhouettes.

From Water Bears to Grizzly Bears: Unusual Animal Models

Taconic Biosciences
Sex Differences in Neurological Research

Sex Differences in Neurological Research

bit.bio logo
New Frontiers in Vaccine Development

New Frontiers in Vaccine Development

Sino

Products

Tecan Logo

Tecan introduces Veya: bringing digital, scalable automation to labs worldwide

Explore a Concise Guide to Optimizing Viral Transduction

A Visual Guide to Lentiviral Gene Delivery

Takara Bio
Inventia Life Science

Inventia Life Science Launches RASTRUM™ Allegro to Revolutionize High-Throughput 3D Cell Culture for Drug Discovery and Disease Research

An illustration of differently shaped viruses.

Detecting Novel Viruses Using a Comprehensive Enrichment Panel

Twist Bio&nbsp;