2. Academic Validation
  3. Calcineurin controls proximodistal blastema polarity in zebrafish fin regeneration

Calcineurin controls proximodistal blastema polarity in zebrafish fin regeneration

  • Proc Natl Acad Sci U S A. 2021 Jan 12;118(2):e2009539118. doi: 10.1073/pnas.2009539118.
Zigang Cao 1,  Yunlong Meng 2,  Fanghua Gong 3,  Zhaopeng Xu 2,  Fasheng Liu 1,  Mengjie Fang 1,  Lufang Zou 1,  Xinjun Liao 1,  Xinjuan Wang 4,  Lingfei Luo 4,  Xiaokun Li 3,  Huiqiang Lu 5 2
Affiliations

Affiliations

  • 1 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an, 343009 Jiangxi, China.
  • 2 Center for Drug Screening and Research, School of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, 341000 Jiangxi, China.
  • 3 School of Pharmacy, Wenzhou Medical University, Wenzhou, 325000 Zhejiang, China.
  • 4 Institute of Developmental Biology and Regenerative Medicine, Southwest University, Beibei, 400715 Chongqing, China.
  • 5 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an, 343009 Jiangxi, China; luhq2@126.com.
PMID: 33376206 DOI: 10.1073/pnas.2009539118
Abstract

Planarian flatworms regenerate their heads and tails from anterior or posterior wounds and this regenerative blastema polarity is controlled by Wnt/β-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.

Keywords

calcineurin; fin regeneration; polarity; zebrafish.

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