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An endogenous scaling mechanism in zebrafish appendages that controls two-pore potassium-leak channel activity to regulate morphogen and growth factor transcription

Chao Yi, Tim WGM Spitters, Ezz Al-Din Ahmed Al-Far, Sen Wang, Simian Cai, Xin Yan, Kaomei Guan, Michael Wagner, Ali El-Armouche, Christopher L. Antos
doi: https://doi.org/10.1101/2020.07.03.186403
Chao Yi
1School of Life Sciences and Technology, ShanghaiTech University, 230 Haike Road, Shanghai, People’s Republic of China
2CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences
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Tim WGM Spitters
1School of Life Sciences and Technology, ShanghaiTech University, 230 Haike Road, Shanghai, People’s Republic of China
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Ezz Al-Din Ahmed Al-Far
3Institut für Pharmakologie und Toxikologie, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
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Sen Wang
1School of Life Sciences and Technology, ShanghaiTech University, 230 Haike Road, Shanghai, People’s Republic of China
2CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences
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Simian Cai
1School of Life Sciences and Technology, ShanghaiTech University, 230 Haike Road, Shanghai, People’s Republic of China
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Xin Yan
1School of Life Sciences and Technology, ShanghaiTech University, 230 Haike Road, Shanghai, People’s Republic of China
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Kaomei Guan
3Institut für Pharmakologie und Toxikologie, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
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Michael Wagner
3Institut für Pharmakologie und Toxikologie, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
4Abteilung für Rhythmologie, Herzzentrum Dresden, Technische Universität Dresden, Fetscherstraße 76, 01307 Dresden, Germany
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Ali El-Armouche
3Institut für Pharmakologie und Toxikologie, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
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Christopher L. Antos
1School of Life Sciences and Technology, ShanghaiTech University, 230 Haike Road, Shanghai, People’s Republic of China
3Institut für Pharmakologie und Toxikologie, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany
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  • For correspondence: clantos@shanghaitech.edu.cn christopher.antos@tu-dresden.de
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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 development programs, including two morphogen pathways involved in tissue formation, shh and wnt signaling. We provide in vivo transplantation evidence that the activation of developmental programs is cell autonomous and Kcnk5b can induce the expression of these developmental programs in cultured mammalian cell lines. We also demonstrate how post-translational modification of serine 345 in Kcnk5b by calcineurin regulates channel activity and controls these developmental programs to scale the fin. Thus, we show how an endogenous bioelectric program is regulated and promotes coordinated developmental signaling to generate and scale a vertebrate appendage.

Competing Interest Statement

The authors have declared no competing interest.

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Posted July 04, 2020.
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An endogenous scaling mechanism in zebrafish appendages that controls two-pore potassium-leak channel activity to regulate morphogen and growth factor transcription
Chao Yi, Tim WGM Spitters, Ezz Al-Din Ahmed Al-Far, Sen Wang, Simian Cai, Xin Yan, Kaomei Guan, Michael Wagner, Ali El-Armouche, Christopher L. Antos
bioRxiv 2020.07.03.186403; doi: https://doi.org/10.1101/2020.07.03.186403
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An endogenous scaling mechanism in zebrafish appendages that controls two-pore potassium-leak channel activity to regulate morphogen and growth factor transcription
Chao Yi, Tim WGM Spitters, Ezz Al-Din Ahmed Al-Far, Sen Wang, Simian Cai, Xin Yan, Kaomei Guan, Michael Wagner, Ali El-Armouche, Christopher L. Antos
bioRxiv 2020.07.03.186403; doi: https://doi.org/10.1101/2020.07.03.186403

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