The Regenerative Capacity of the Zebrafish Caudal Fin Is Not Affected by Repeated Amputations

TLDR

Zebrafish can regenerate many tissues, and the caudal fin is a convenient, rapidly regenerating tissue that is easy to study experimentally. The study investigates whether repeated fin amputations and manipulations that block regeneration affect the zebrafish caudal fin’s regenerative capacity. Repeated amputations do not impair regeneration, while transient inhibition of Wnt/β‑catenin signaling blocks outgrowth but is fully reversible upon re‑amputation, indicating the caudal fin possesses an essentially unlimited regenerative capacity independent of Wnt/β‑catenin‑dependent stem cell survival.

Abstract

The zebrafish has the capacity to regenerate many tissues and organs. The caudal fin is one of the most convenient tissues to approach experimentally due to its accessibility, simple structure and fast regeneration. In this work we investigate how the regenerative capacity is affected by recurrent fin amputations and by experimental manipulations that block regeneration.We show that consecutive repeated amputations of zebrafish caudal fin do not reduce its regeneration capacity and do not compromise any of the successive regeneration steps: wound healing, blastema formation and regenerative outgrowth. Interfering with Wnt/ß-catenin signalling using heat-shock-mediated overexpression of Dickkopf1 completely blocks fin regeneration. Notably, if these fins were re-amputated at the non-inhibitory temperature, the regenerated caudal fin reached the original length, even after several rounds of consecutive Wnt/ß-catenin signalling inhibition and re-amputation.We show that the caudal fin has an almost unlimited capacity to regenerate. Even after inhibition of regeneration caused by the loss of Wnt/ß-catenin signalling, a new amputation resets the regeneration capacity within the caudal fin, suggesting that blastema formation does not depend on a pool of stem/progenitor cells that require Wnt/ß-catenin signalling for their survival.