Denervation impairs regeneration of amputated zebrafish fins

TLDR

Zebrafish can regenerate many tissues, and in amphibians nerve fibers at injury sites are thought to release factors that sustain blastemal proliferation, but the underlying molecular mechanisms remain unclear. This study uses zebrafish to investigate how nerve fibers influence pectoral fin regeneration. The authors performed pectoral fin denervation followed by amputation and examined the regenerative response under these conditions. Denervation allowed wound closure but prevented apical epithelial cap formation, blastema development, and outgrowth, while altering expression of key Fgf, Wnt, and Shh genes, demonstrating that proper innervation is essential for successful fin regeneration.

Abstract

Zebrafish are able to regenerate many of its tissues and organs after damage. In amphibians this process is regulated by nerve fibres present at the site of injury, which have been proposed to release factors into the amputated limbs/fins, promoting and sustaining the proliferation of blastemal cells. Although some candidate factors have been proposed to mediate the nerve dependency of regeneration, the molecular mechanisms involved in this process remain unclear. We have used zebrafish as a model system to address the role of nerve fibres in fin regeneration. We have developed a protocol for pectoral fin denervation followed by amputation and analysed the regenerative process under this experimental conditions. Upon denervation fins were able to close the wound and form a wound epidermis, but could not establish a functional apical epithelial cap, with a posterior failure of blastema formation and outgrowth, and the accumulation of several defects. The expression patterns of genes known to be key players during fin regeneration were altered upon denervation, suggesting that nerves can contribute to the regulation of the Fgf, Wnt and Shh pathways during zebrafish fin regeneration. Our results demonstrate that proper innervation of the zebrafish pectoral fin is essential for a successful regenerative process, and establish this organism as a useful model to understand the molecular and cellular mechanisms of nerve dependence, during vertebrate regeneration.