Regeneration has long attracted biomedical interest because of the potential of replacing damaged organs with new ones. However, why some lower vertebrates (e.g., fish and salamanders) regenerate extensively while others such as mammals regenerate poorly is not well understood. Further, the ability to regenerate damaged organs displays progressive decline during aging, leading to reduced quality of life in old animals. How the regenerative capacities are lost during evolution and aging is still a long-standing question in biology. Powered with a new genetic model, the African killifish Nothobranchius furzeri, the Wang Lab is interested in identifying molecular mechanisms of regenerative capacities that can be targeted to help human to rebuild damaged organs. Our current research will focus on, but not limited to, the following areas:
(1) The molecular basis of aging-dependent loss of regenerative capacity in African killifish spinal cords.
(2) Understanding mechanisms underpinning the activation of injury-response and regeneration-response.
(3) Genetic mechanisms responsible for the loss of regenerative capacities during evolution.
The African killifish inhabit temporal ponds subjected to annual desiccation in the southeast of Africa. The adult fish are only present in the rainy season when the ponds are filled with water. The African killifish survive the dry season as diapause embryos buried in the mud, waiting for the next rainy season to hatch and reproduce again. The strong selective pressures have driven this species to evolve unique features that can expedite organ development-, regeneration- and aging-related studies including 1) a remarkably short generation time (30-45 days); 2) diapause embryos that allow for convenient maintenance and storage of strains/lines in dry Petri Dishes for years ; 3) rapid aging under laboratory conditions (a median lifespan of 4-6 months); and 4) highly efficient genetic manipulations with CRISPR/Cas9, Tol2-mediated transgenesis, and PhiC31-mediated site-specific transgenesis because of the slow embryonic development. African killifish provide a unique opportunity to explore adult regeneration and aging much faster than what is possible with other model organisms.