Recent discoveries indicate that in certain organisms, injuries to one part of the body can trigger a healing response in another area, challenging the belief that this phenomenon is merely a side effect. When a mouse sustains an injury to one leg, stem cells in the other leg become activated, preparing for potential healing. Similarly, axolotls, known for their remarkable limb regeneration abilities, exhibit a similar response. In zebrafish, heart injuries can lead to specific changes in distant organs like the kidney and brain. Bo Wang, an assistant professor of bioengineering at Stanford, stated, “In many different organisms, you can see the whole body respond to an injury. But whether or not those responses actually have any function has been unclear. So that’s what we’re focusing on.”
In a recent publication in the journal Cell, Wang and his team have shed light on the importance of this whole-body coordination in wound healing and subsequent tissue regeneration in planarian worms. Understanding the mechanisms that trigger and control regeneration, as well as how it is coordinated, provides valuable insights for studying cancer, often viewed as persistent wounds that don’t heal.
Planarian worms, half-inch-long flatworms with exceptional regenerative abilities, were the focus of Wang’s research. When injured, these worms display responses in distant tissues, suggesting a coordinated reaction. Wang aimed to comprehend how these responses were orchestrated. One potential mechanism under investigation was the extracellular signal-related kinase (ERK) pathway, through which cells communicate and propagate signals like a wave. However, previous research had indicated that ERK waves moved too slowly to be effective. Wang found that ERK waves traveled significantly faster than previously observed, utilizing special body-wall muscle cells as “superhighways,” transmitting signals from one end of the body to another in a matter of hours, rather than days.
To test the role of ERK waves in coordinating distant healing responses, Yuhang Fan, a graduate student in Wang’s lab, conducted experiments on planarians by blocking the ERK signal to the back half of the organism after decapitation. This intervention resulted in a failure of the head to regrow, demonstrating the vital role of ERK waves in coordinating regeneration. Interestingly, it was also found that the timing of amputations affected the regeneration process, suggesting a sort of “global body voting system” that determines when regeneration should occur.
Understanding the extraordinary regenerative abilities observed in certain animals, such as planarians, sea stars, and axolotls, compared to the limited regenerative capacity in humans, has significant implications for medical advancements. By investigating the genes and mechanisms involved in regeneration, researchers hope to unlock potential treatments and interventions, including addressing issues related to cancer. The study’s findings offer a pathway to explore these shared genes and their role in controlled tissue regeneration and its association with cancer.