Regeneration of Fins and Limbs Relies on a Shared Cellular Playbook

United States - Ekhbary News Agency

Regeneration of Fins and Limbs Relies on a Shared Cellular Playbook

In a discovery that deepens our understanding of biological regeneration, scientists have identified a common cellular and genetic "toolkit" that allows certain vertebrates to regrow lost fins and limbs. The research, published in Nature Communications, focuses on the Senegal bichir, the axolotl salamander, and the zebrafish, showcasing remarkable regenerative abilities that offer crucial insights into the early evolutionary history of this phenomenon across the animal kingdom.

The Senegal bichir (Polypterus senegalus), a fish considered a "living fossil" due to its retention of ancient traits, serves as a prime model organism for regeneration studies. This species possesses the extraordinary ability to regrow entire fins after amputation, making it a vital subject for understanding the origins of limb regeneration. As it resides at the base of the modern bony fish evolutionary tree, the bichir provides a unique window into the ancient development of regenerative capabilities.

Led by evolutionary developmental biologist Igor Schneider of Louisiana State University, the research team investigated these mechanisms. They meticulously tracked gene activity at the wound sites of bichir fins after amputation, comparing this data with similar new and existing datasets from the axolotl, renowned for its limb regeneration, and the zebrafish, which can regenerate the bony tips of its fins. This comparative approach aimed to pinpoint conserved cellular and molecular processes.

The study revealed a critical role for immune cells in the initial stages of regeneration across all three species. Upon wounding, immune cells swiftly migrate to the injury site. While their first task is to combat potential bacterial infections—a typical response seen even in humans—in the bichir and axolotl, these cells quickly shift function. They actively dampen inflammatory responses that could otherwise lead to scar tissue formation, thereby facilitating a smoother regenerative process.

Disruption of blood supply and oxygen flow is a common challenge in wound healing. The new data clarifies how these species overcome this obstacle. A variety of cells within the wound site began producing energy through an oxygen-independent metabolic pathway. This self-sufficient energy production fuels the proliferation of new cells and the synthesis of essential proteins and other materials required for the complex process of regeneration.

Another surprising finding was the appearance of myoglobin, a protein crucial for oxygen storage in muscles, within skin cells covering the wound areas in the fish. Even more unexpectedly, red blood cells surged to the amputation sites in the bichir and axolotl, eventually constituting up to 20% of all cells at the wound site. This is a dramatic increase from their typical representation of less than 2% in uninjured fin or limb tissue.

Unlike mature human red blood cells, which lack nuclei, the red blood cells in both the bichir and axolotl retain their nuclei. Within these nuclei, the researchers observed a significant upregulation of genes involved in regulating immune responses and monitoring oxygen levels following amputation. Dr. Schneider suggests it is "enticing to think" these nucleated red blood cells might be providing instructive signals to other cells, thereby helping to coordinate the regeneration cascade.

Concurrently, genes associated with limb development and DNA repair were activated. Furthermore, two distinct populations of repair cells emerged: one near the base of the regenerating structure and another near the tip. This comprehensive coordination represents a "big step" in understanding how regeneration is orchestrated, according to developmental biologist Ji-Feng Fei, who was not involved in the study. The shared regenerative mechanisms across species that diverged approximately 400 million years ago underscore the ancient origins of this remarkable biological ability.

Dr. Schneider hopes to further explore regeneration by conducting similar studies in lizards, which can regenerate their tails but not limbs. He humorously notes that perhaps Spider-Man's nemesis in the movie might have been more successful with salamander DNA if his goal was limb regrowth, unless he specifically intended to regenerate a tail.

Ekhbary News Agency