Project 12: The role and regulation of reactive oxygen species (ROS) during appendage and organ regeneration

The goal of this project is to identify the downstream targets of reactive oxygen species (ROS) during appendage regeneration in zebrafish. For many years, my research group has been investigating the molecular and cellular mechanisms involved in tissue formation, repair and regeneration in Xenopus and zebrafish, two vertebrate model organisms with high regenerative capacity. Recent work from my laboratory has revealed the importance of sustained reactive oxygen species (ROS) during appendage regeneration and embryonic development^1–3. Furthermore, our findings suggest that elevated ROS levels promote cell proliferation, growth factor signalling and metabolism; processes essential for regeneration. This project will expand upon these findings by identifying the critical downstream targets of adult caudal fin regeneration and heart regeneration in zebrafish, with a particular emphasis on the family of protein tyrosine phosphatases.⁴

1. Love, N.R., Chen, Y., Ishibashi, S., Kritsiligkou, P., Lea, R., Koh, Y., Gallop, J.L., Dorey, K., and Amaya, E. (2013). Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration. Nat Cell Biol 15, 222–228. 10.1038/ncb2659.
2. Han, Y., Ishibashi, S., Iglesias-Gonzalez, J., Chen, Y., Love, N.R., and Amaya, E. (2018). Ca2+-Induced Mitochondrial ROS Regulate the Early Embryonic Cell Cycle. Cell Reports 22, 218–231. 10.1016/j.celrep.2017.12.042.
3. Chopra, K., Folkmanaitė, M., Stockdale, L., Shathish, V., Ishibashi, S., Bergin, R., Amich, J., and Amaya, E. (2023). Duox is the primary NADPH oxidase responsible for ROS production during adult caudal fin regeneration in zebrafish. iScience, 106147. 10.1016/j.isci.2023.106147.
4. Helston, O., and Amaya, E. (2021). Reactive oxygen species during heart regeneration in zebrafish: Lessons for future clinical therapies. Wound Repair Regen 29, 211–224. 10.1111/wrr.12892.