Biosciences Research Seminar - A conserved role for reactive oxygen species and metabolic reprogramming during early embryonic development and appendage regeneration

We are interested in uncovering the key cellular and molecular mechanisms underlying appendage regeneration in zebrafish and Xenopus. We have previously shown that tadpole tail regeneration requires a sustained production of reactive oxygen species (ROS). We also found that sustained and elevated ROS levels are necessary for cell proliferation and growth factor signaling during tail regeneration. Intriguingly, we have also found that fertilization induces rapid increase in ROS levels, which oscillate with the cell cycle and are also sustained throughout early embryogenesis. If we inhibit or attenuate ROS production following fertilization, cell cycle progression and growth factor signaling are inhibited or attenuated, respectively. Furthermore, we found that not only ROS levels oscillate, but cellular metabolism oscillates between a Warburg-like metabolism and a non-Warburg-like metabolism with each cell cycle. We also found that a similar metabolic switch occurs following larval fin amputations in zebrafish, and this switch is necessary for wound contraction and larval tail regeneration to proceed, but not larval fin regeneration. Thus, we find many remarkable parallels in the induction, maintenance and roles for ROS and metabolic reprogramming during early embryonic development and during appendage regeneration. Indeed, both injury and fertilization seem to set in motion a similar series of events, and as such, we have begun to think of fertilization as an injury, which induces development, in much the same way that injury induces a regenerative response in post-embryonic stages. Thus, we postulate that a successful regenerative response is dependent on a return to an embryonic-like state of cellular oxidation and metabolism, which facilitates tissue formation, repair and regeneration.