A calcineurin-mediated scaling mechanism that controls a K+-leak channel to regulate morphogen and growth factor transcription

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Abstract

The increase in activity of the two-pore potassium-leak channel Kcnk5b maintains allometric juvenile growth of adult zebrafish appendages. However, it remains unknown how this channel maintains allometric growth and how its bioelectric activity is regulated to scale these anatomical structures. We show the activation of Kcnk5b is sufficient to activate several genes that are part of important development programs. We provide in vivo transplantation evidence that the activation of gene transcription is cell autonomous. We also show that Kcnk5b will induce the expression of different subsets of the tested developmental genes in different cultured mammalian cell lines, which may explain how one electrophysiological stimulus can coordinately regulate the allometric growth of diverse populations of cells in the fin that use different developmental signals. We also provide evidence that the post-translational modification of serine 345 in Kcnk5b by calcineurin regulates channel activity to scale the fin. Thus, we show how an endogenous bioelectric mechanism can be regulated to promote coordinated developmental signaling to generate and scale a vertebrate appendage.

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All data generated are included in the manscript and files

Article and author information

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Chao Yi

School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Tim WGM Spitters

School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China

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The authors declare that no competing interests exist.
Ezz Al-Din Ahmed Al-Far

Institut fuer Pharmakologie und Toxikologie, Technische Universitaet Dresden, Dresden, Germany

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The authors declare that no competing interests exist.
Sen Wang

School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China

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The authors declare that no competing interests exist.
TianLong Xiong

School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Simian Cai

School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China

Competing interests
The authors declare that no competing interests exist.
Xin Yan

School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China

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The authors declare that no competing interests exist.
Kaomei Guan

Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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The authors declare that no competing interests exist.
Michael Wagner

Department for Rhythmology, Technische Universitaet Dresden, Dresden, Germany

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The authors declare that no competing interests exist.
Ali El-Armouche

Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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The authors declare that no competing interests exist.
Christopher L Antos

School of Life Sciences and Technology, ShanghaiTech University, Shanghai, China

For correspondence
clantos@shanghaitech.edu.cn

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8881-8568

Funding

Deutsche Forschungsgemeinschaft (AN 797/4-1)

Christopher L Antos

ShanghaiTech University

Christopher L Antos

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with guidelines for the care and use of laboratory animals for the European Union, Germany,Landesdirektion Sachsen, the Technische Universität Dresden, China and ShanghaiTech University. The protocols were approved by the Landesdirektion Sachsen (Permit number: DD24.1-5131/394/79) and the Shanghaitech Ethical Use of Aminals Committee (20200903003) All procedures using zebrafish were performed under Tricane anesthesia, and every effort was made to minimize discomfort and suffering.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.