Some species, like the starlet sea anemone, have the impressive ability to regenerate large portions of their bodies even after severe injuries. Research has revealed that this regenerative process involves cells and molecules in parts of the body that are far from the injury, all aimed at restoring the original shape of the animal. This study highlights the essential role of maintaining body shape in animals and deepens our understanding of the molecular pathways that govern regeneration.
Our bodies adapt in amazing ways to changing environments. For instance, regardless of whether it’s hot in summer or freezing in winter, our internal temperature stays around 37°C due to a process known as homeostasis. This unseen balancing act is crucial for survival, allowing animals to keep stable internal conditions even when the outside world fluctuates. Recent findings from the Ikmi Group at EMBL Heidelberg indicate that homeostasis may extend beyond internal regulation and actively reshape an organism’s form.
The starlet sea anemone (Nematostella vectensis) is known for its extraordinary regenerative capabilities. If its head or foot is removed, it simply grows a new one. If it is cut in half, both halves regenerate into complete, functional anemones.
Unlike some regenerative animals, such as salamanders and fish, which focus on rebuilding lost parts proportional to what remains, this sea anemone takes a unique approach. It reshapes its entire body to keep the same overall form, even if that involves altering uninjured parts. This trait can also be observed in flatworms and other organisms capable of whole-body regeneration.
“Regeneration is fundamentally about restoring function after tissue loss or injury,” said Aissam Ikmi, Group Leader at EMBL and senior author of the new study published in the journal Developmental Cell. “Most studies generally look at patterns and sizes in regeneration, but our results indicate that preserving shape is also essential — and is something the organism actively manages.”
The discovery was sparked when Stephanie Cheung, a doctoral researcher in Ikmi’s group, noticed an anomaly. After an injury to the foot of a sea anemone, she found not just cell division at the injury site but also unexpected division occurring at the mouth area, the opposite end of the body. This indicated that the sea anemone was transmitting signals throughout its body in response to the injury.
To further investigate this phenomenon, the research team employed a technique called spatial transcriptomics alongside sophisticated imaging methods. This allowed them to identify which genes were active in various parts of the anemone’s body during the regeneration process. Their findings were unexpected: the injury prompted molecular changes in areas both close and distant from the wound. Cells migrated and tissues rearranged, effectively reshaping the entire organism.
Interestingly, the degree of body reshaping was influenced by the severity of the injury. A loss of a foot caused only minor adjustments, while being cut in half led to extensive remodeling. The researchers identified a group of enzymes known as metalloproteases which became increasingly active as more tissue was lost. These enzymes operated not only at the wound site but also throughout the entire body, assisting in tissue realignment.
“This is the first time metalloprotease activity has been documented in animals like this,” said Petrus Steenbergen, one of the lead authors and a Senior Research Technician in Ikmi’s group. “I had to create and refine experimental conditions specifically for Nematostella, as there was limited information available for other species. It took some time, but the resulting findings were very fulfilling.”
The breakthrough occurred when the researchers recognized that all these alterations aimed to return the anemone to its original shape. By calculating the aspect ratio — the relationship between length and width — they discovered that the anemone reverted to its pre-injury proportions. Thus, even if it shrank post-injury, it preserved its overall shape.
“We could observe the body-wide coordination driving this remodeling,” Ikmi said. “This proportional response allows the anemone to restore its shape, illustrating how organisms like Nematostella perceive and respond to tissue loss in a scale appropriate to the damage incurred.”
This research was a collaborative initiative. Rik Korswagen’s team from the Hubrecht Institute in the Netherlands helped to implement spatial transcriptomics techniques in the sea anemone. Oliver Stegle’s group at EMBL Heidelberg and the German Cancer Research Center (DKFZ) contributed bioinformatics expertise and statistical methods needed to analyze the spatial gene expression data.
“It was exciting to collaboratively decipher the findings of this study by combining our expertise in data analysis and cell biology,” said Tobias Gerber, another lead author of the study. “This project was a truly cooperative experience, and I’m delighted to have been a part of it.”
Looking forward, Ikmi and his team are eager to investigate further questions. “The next important question is why maintaining shape is so vital,” Ikmi said. “And how does the organism perceive its own shape? What allows it to know what it currently looks like?”
Using the remarkable starlet sea anemone as their model, they are excited to reveal more insights about how organisms heal and maintain equilibrium.
