In the vast ocean, sea urchin larvae, though tiny and delicate, possess an extraordinary ability to heal themselves. This remarkable process, involving the coordinated efforts of pigment and blastocoelar cells, is the focus of groundbreaking research in the McClay Lab at Duke University. In 2022, a study by Dr. David R. McClay, Arthur S. Pearse Professor Emeritus of Biology at Duke University, and his team shed light on the intricate mechanisms of wound repair in these fascinating marine organisms, offering insights that could have far-reaching implications for understanding immune responses and tissue regeneration in higher organisms, including humans. 

Above: Sea urchin. Image courtesy of Ralph Clevenger via National Geographic. 

The study of wound repair in sea urchin larvae is part of a larger quest to unravel the secrets of innate immunity and tissue regeneration. By exploring how these larvae use their immune system to repair wounds, researchers hope to gain a deeper understanding of the evolution of immune responses. Because they share a common ancestor with humans as deuterostomes, sea urchins are an ideal model for studying the origins and development of immune systems. This research enhances the field of developmental biology by helping scientists understand vertebrate cell lineage and its diverse adaptive immune responses.  

Sea urchin larvae are equipped with two main types of immune cells: pigment cells and blastocoelar cells. These cell types play crucial roles in the larvae’s ability to respond to injuries and infections. When activated by calcium transients, pigment cells migrate to the wound site and release echinochrome A, a substance with bactericidal and antiviral properties. Blastocoelar cells, on the other hand, are involved in various functions, including remodeling the skeleton if it protrudes through the epithelium.  

Above: A calcium transient is rapidly introduced by a wound and spreads across the epithelium, activating pigment cells to migrate toward the wound site. Image courtesy of Allen et al., 2022.  

To investigate these cellular processes, the researchers employed a variety of techniques. The team used mechanical and laser-induced wounding assays to create controlled injuries in the larvae, allowing the researchers to observe the immediate and subsequent cellular responses. In addition, the team used calcium imaging, which relies on the injection of a calcium-sensitive dye, to visualize and track calcium waves in response to wounding.

When a fire breaks out, an alarm system is activated in a firehouse, sending a rapid signal to alert firefighters to respond. Similarly, in response to a wound in the sea urchin larvae, calcium transients activate pigment cell migration. To confirm the necessity of calcium channels for the transient, the researchers used verapamil, a calcium channel inhibitor. When they applied verapamil, the calcium transient did not propagate, and the pigment cells failed to initiate their directed movement toward the wound site. This inhibition demonstrated that the calcium transient is crucial for activating pigment cell migration. In contrast, blastocoelar cells continued to move even in the presence of verapamil, indicating that their activation mechanism is independent of the calcium transient.  

One of the most striking discoveries of this study is the rapid and directional migration of pigment cells towards the wound site. Within seconds of an injury, a calcium transient spreads across the epithelium, activating the pigment cells to move toward the wound. This movement is crucial for effective wound repair, as the pigment cells release echinochrome A to combat potential infections. The blastocoelar cells then wrap around the protruding skeletal tips and participate in their excision, allowing the epithelium to seal the wound. Interestingly, Dr. McClay and his team found that wound repair can still occur without pigment cells, suggesting that blastocoelar cells and other mechanisms can compensate for their absence. While blastocoelar cells were previously known to be involved in skeletal remodeling, this study provides new insights into their specific role in wound repair. The researchers discovered that blastocoelar cells not only assist in excising protruding skeletal tips but also contribute to the rapid sealing of the wound.  

With over sixty years of research experience, Dr. McClay has dedicated his career to studying developmental biology. His passion for understanding the fundamental processes of life has driven his pursuits. Dr. McClay’s research, particularly on sea urchin larvae, unveils the intricate mechanisms of wound repair and immune responses. This study not only advances the knowledge of developmental biology but also opens new avenues for medical research. By understanding the immune responses and wound-healing processes in these tiny marine organisms, researchers can gain valuable insights into the evolution of immune systems and identify potential targets for therapeutic interventions in humans. The journey of these larvae, from injury to healing, highlights the remarkable resilience of life and the intricate dance of cells that keep organisms healthy and thriving.