Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 2, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2009539118
Keywords
calcineurin; polarity; fin regeneration; zebrafish
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Funding
- National Key R&D Program of China [2018YFA0801000]
- National Natural Science Foundation [31771606, 31900597, 81860282, 81660087]
- Natural Science Foundation Project of Jiangxi Province [20192ACB21013, 2018ACB21033]
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This study reveals that calcineurin inhibition can induce proximal growth of regeneration blastema in zebrafish fins, establishing calcineurin as a molecular switch for specifying the blastema of the proximodistal axis in fin regeneration polarity.
Planarian flatworms regenerate their heads and tails from anterior or posterior wounds and this regenerative blastema polarity is controlled by Wnt/beta-catenin signaling. It is well known that a regeneration blastema of appendages of vertebrates such as fish and amphibians grows distally. However, it remains unclear whether a regeneration blastema in vertebrate appendages can grow proximally. Here, we show that a regeneration blastema in zebrafish fins can grow proximally along the proximodistal axis by calcineurin inhibition. We used fin excavation in adult zebrafish to observe unidirectional regeneration from the anterior cut edge (ACE) to the posterior cut edge (PCE) of the cavity and this unidirectional regeneration polarity occurs as the PCE fails to build blastemas. Furthermore, we found that calcineurin activities in the ACE were greater than in the PCE. Calcineurin inhibition induced PCE blastemas, and calcineurin hyperactivation suppressed fin regeneration. Collectively, these findings identify calcineurin as a molecular switch to specify the PCE blastema of the proximodistal axis and regeneration polarity in zebrafish fin.
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