Abstract
BackgroundThe 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.Methodology/Principal FindingsWe 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.Conclusions/SignificanceWe 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.
Highlights
In contrast to humans, some organisms retain the extraordinary capacity to regenerate throughout adult life
This led the authors to propose that regeneration of the spinal cord in Triturus carnifex relies on differentiated cells present in the stump that dedifferentiate contributing to the regenerate
It was shown that the regenerative capacity of the zebrafish caudal fin does not decline when amputated up to 9 times
Summary
Some organisms retain the extraordinary capacity to regenerate throughout adult life. One of such organisms is the zebrafish, a vertebrate that is able to regenerate fins, scales, retina, spinal cord and heart among other internal organs [1]. Its fast and robust regeneration and its simple architecture, the zebrafish caudal fin is one of the most powerful models for regenerative studies. The caudal fin is composed of several segmented bony rays and inter-ray mesenchymal tissue, all enclosed by an epidermis. 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
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