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Unveiling the Regenerative Secrets of the Starlet Sea Anemone
The human body showcases impressive adaptability in response to environmental changes, managing to keep its core temperature stable at around 37°C through homeostasis. This essential balancing act aids survival, allowing organisms to maintain internal order despite fluctuating external conditions. Recent findings from the Ikmi Group at EMBL Heidelberg suggest that homeostasis might extend beyond inner stability and play a significant role in reshaping an organism’s structure.
The starlet sea anemone (Nematostella vectensis) is renowned for its extraordinary regenerative properties. When its head or foot is severed, it can regenerate these body parts seamlessly. Furthermore, if the anemone is halved, each segment can independently develop into a fully functional organism.
In contrast to other regenerative species like salamanders and fish, which tend to restore lost limbs in scale with the remaining parts, the starlet sea anemone uniquely reconfigures its entire structure to preserve its original form. This phenomenon is also observed in flatworms and other creatures with comprehensive regenerative abilities.
“Regeneration focuses on restoring functionality after tissue damage,” explained Aissam Ikmi, Group Leader at EMBL and a main author of the recent study published in Developmental Cell. “While most regeneration research emphasizes size and pattern, our work reveals that maintaining an organism’s shape is a vital aspect, actively governed by the organism itself.”
The research initiative took off when Stephanie Cheung, a doctoral student in Ikmi’s lab, noticed an unexpected cellular activity: after a sea anemone’s foot was injured, she recorded cell division not only at the injury site but also at the opposite end, around the mouth. This observation indicated that the anemone was likely communicating signals throughout its body in reaction to the injury.
To delve deeper, the research team employed spatial transcriptomics alongside advanced imaging techniques, enabling them to investigate gene activity across different body regions during the regeneration process. The results were intriguing: injury induction prompted molecular changes near and distant from the site of the wound. This led to cellular movement and tissue reorganization, indicating a holistic reshaping of the organism.
Interestingly, the degree of anatomical reshaping was directly proportional to the severity of the injury. A foot loss elicited minor adjustments, whereas cutting the anemone in half resulted in substantial remodeling. The researchers identified a group of enzymes known as metalloproteases, which became increasingly active with greater tissue loss. Notably, these enzymes were active throughout the organism, facilitating tissue realignment.
“The involvement of metalloprotease activity in such a context has not been previously observed in similar animals,” remarked Petrus Steenbergen, a lead author of the study and a Senior Research Technician in Ikmi’s group. “Creating the experimental conditions tailored for Nematostella was a challenge due to limited prior studies on related species, but the results proved to be gratifying.”
The pivotal discovery was that all the observed changes worked towards restoring the anemone’s original contour. By assessing the aspect ratio—comparing length to width—the researchers found that the anemone consistently returned to its pre-injury shape, regardless of any decrease in size following injury.
“We could see the extensive coordination that orchestrates this remodeling process,” Ikmi stated. “This proportionality in response enables the anemone to re-establish its shape, underscoring the sophisticated way organisms like Nematostella perceive and react to tissue loss relative to the extent of the damage endured.”
This research was a collaborative venture, with Rik Korswagen’s team at the Hubrecht Institute in the Netherlands contributing to the application of spatial transcriptomics in the study of sea anemones. Additionally, bioinformatics experts from Oliver Stegle’s team at EMBL Heidelberg and the German Cancer Research Center (DKFZ) aided in developing statistical methodologies for analyzing the spatial gene expression data.
“Working together to decode the research findings was a rewarding endeavor, as we merged data analysis skills with cell biology expertise,” expressed Tobias Gerber, another lead author of the study. “This project truly exemplified collaborative research, and I am proud to have participated.”
Looking forward, Ikmi and his team are eager to tackle new inquiries. “One of the upcoming questions is to understand why maintaining shape holds such significance,” Ikmi stated. “How does the organism gauge its own shape? What mechanisms enable it to ascertain its physical appearance?”
With the remarkable starlet sea anemone as their key focus, the team is poised to expand their understanding of organismal healing and the maintenance of balance within biological systems.
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