Regeneration in the zebrafish model system
Mammalian tissues achieve remarkable feats of regeneration. After removal of more than two-thirds of its mass, the liver rapidly regenerates within several days by hepatocyte proliferation. Multipotent hematopoietic stem cells replenish red and white blood cells, and skin, muscle, and intestine are repaired by tissue-specific stem cells. However, this regenerative capacity is distributed unequally among mammalian organs: limbs, brain, spinal cord, and heart display minimal regeneration after tissue damage or loss. How and why tissue regeneration does (or does not) occur are critical questions; the answers have the potential to impact the clinical outcomes of the many diseases of organ damage, including heart failure, Alzheimer’s disease, and diabetes. It has been known for centuries that certain non-mammalian vertebrates, such as urodele amphibians and teleost fish, regenerate complex tissues much more effectively than mammals. Salamanders have long been the central characters employed in vertebrate regeneration studies. Two features make the teleost zebrafish a powerful, complementary model system to study organ regeneration. First, they are highly regenerative, equipped to regrow amputated fins, injured retinae, transected optic nerves and spinal cord, and resected heart muscle. Second, unlike salamanders, they are amenable to both forward and reverse genetic approaches. As is customary with genetic model systems, a wide array of community resources is available for gene discovery and molecular characterization in zebrafish, including mutagenesis screens, transgenesis, microarrays, developmental markers, and genome sequence information. The Poss lab is investigating the biology of spectacular regenerative events in zebrafish to discover new cellular mechanisms, and we are also developing new tools to interrogate regeneration deeply at the molecular level. Over the next several years, we will pursue fundamental aspects of organ regeneration—most importantly, how tissue renewal is stimulated by injury, and how newly created cells recognize position and functionally incorporate into existing tissue.