Molecular and Genetic Analysis of Fin Regeneration in Zebrafish

University Of Wisconsin-Madison, Madison WI

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Abstract

ABSTRACT Regenerative capacity is widespread across almost all animal phyla, but the distributing pattern appears inexplicable. Teleost fishes and urodele amphibians can regenerate amputated appendages, such as fins and limbs, whereas this ability is largely restricted to digit tips in adult mammals. This diverse regenerative distribution raises questions about how animals evolve toward loss or gain of regenerative capacity. This proposal will use zebrafish fins as a model to elucidate cellular and molecular mechanisms controlling regenerative ability. A critical aspect of appendage regeneration is nerve dependence, as denervated appendages display impaired regeneration phenotypes. Previous studies showed that upon injury nerves and their associated Schwann cells provide trophic factors to drive appendage regeneration. However, the accurate reconstruction of nerves during appendage regeneration and their target cells remain unknown. Moreover, the cellular and molecular mechanisms governing production of neurotrophic factors and interaction between nerves and Schwann cells remain elusive. Recent studies also revealed that sensory cells interplay with immune cells and nerves to influence tissue homeostasis and regeneration. Yet, the cross-talks among neuro-immune-sensory cells for appendage regeneration are unexplored. Our research programs will address these key questions in the field of appendage regeneration by employing zebrafish genetic models combined with cellular, molecular, spatial transcriptomic methodologies. First, we will elucidate cellular and molecular mechanisms underlying peripheral nervous system reconstruction and neural modulation of fin regeneration. Second, we will dissect cellular and molecular dynamics that enable special epithelial cells and their interacting partners to engage in neuro-immune- epithelial interactions for fin regeneration. Third, we will utilize MERSCOPE to generate spatial maps detailing the cellular and spatial remodeling processes underlying fin regeneration. The results of these research programs will offer a comprehensive insight into the basic principles of appendage regeneration, providing new avenues to study how innervation, immune cells, and local tissues drive appendage regeneration.