Fyn regeneration

Fyn regeneration T hough all animals do their best to repair injured tissues—closing wounds and mounting an infl am-matory response—some species' repair programs are better than others. Certain amphibians can regrow lost limbs, for example , and zebrafi sh can completely regenerate injured fi ns. How these animals sense the initial wound and induce tissue regener-ation is unclear, however. Yoo et al. identify several zebrafi sh signaling pathways that are only transiently activated immediately after wounding but are essential for the subsequent regeneration of damaged fi ns (1). Anna Huttenlocher and colleagues at the University of Wisconsin-Madison previously found that wounding zebrafi sh larvae induced the generation of reactive oxygen species (ROS), especially hydrogen perox-ide, which activated the Src family kinase (SFK) Lyn in neutrophils (2). " Lyn functions as a redox sensor to detect hydrogen peroxide and direct neutrophils to the wound site, " explains Huttenlocher. " But when we were doing these studies, we noticed that Src family kinases were also activated in the fi n epithelium. So we were interested to see what the signaling [in this tissue] did. " Huttenlocher and colleagues, led by Sa Kan Yoo and Christina Freisinger, found that the activation of epithelial SFKs immediately after wounding was also dependent on ROS (1). Inhibiting the ROS-producing enzyme NADPH oxidase, or depleting the hydrogen per-oxide–generating enzyme dual oxidase, inhibited SFK activation in the epithelia of wounded fi ns. The researchers also identifi ed several other early wound signaling events that occurred independently of ROS and SFKs. Wounding zebrafi sh fi ns stimulated the activation of the kinase ERK in epithelia and, just like in C. elegans (3), induced a burst of calcium release from intracellular stores. " So wounding induces all of these early signals that are very transient, " Huttenlocher says, adding that, because dual oxidase has previously been shown to promote the re-growth of injured tail fi ns (4), " we wanted to address whether these early signaling events impacted fi n regeneration several days later. " Yoo et al. found that blocking ROS production or SFK activity for one hour before and after wounding impaired the regenera-tion of zebrafi sh fi ns three days later. Inhibiting calcium release or ERK signaling had a similar effect. But regeneration was normal if the signaling pathways weren't inhibited until 3–5 hours after wounding, revealing a brief time window in which early wound signals set …