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Bioelectric-calcineurin signaling module regulates allometric growth and size of the zebrafish fin

Jacob M Daane, Jennifer Lanni, Ina Rothenberg, Guiscard Seebohm, Charles W Higdon, Stephen L Johnson, Matthew P Harris
doi: https://doi.org/10.1101/258442
Jacob M Daane
1Department of Genetics, Harvard Medical School; Department of Orthopedic Research, Boston Children’s Hospital, 300 Longwood Avenue, Boston MA 02115;
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Jennifer Lanni
1Department of Genetics, Harvard Medical School; Department of Orthopedic Research, Boston Children’s Hospital, 300 Longwood Avenue, Boston MA 02115;
2Department of Biology, Wheaton College, Norton MA 02766;
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Ina Rothenberg
3Institute for Genetics of Heart Diseases (IfGH), Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany;
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Guiscard Seebohm
3Institute for Genetics of Heart Diseases (IfGH), Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany;
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Charles W Higdon
4Department of Genetics, Washington University Medical School, Saint Louis MO 63110
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Stephen L Johnson
4Department of Genetics, Washington University Medical School, Saint Louis MO 63110
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Matthew P Harris
1Department of Genetics, Harvard Medical School; Department of Orthopedic Research, Boston Children’s Hospital, 300 Longwood Avenue, Boston MA 02115;
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Abstract

The establishment of relative size of organs and structures is paramount for attaining final form and function of an organism. Importantly, variation in the proportions of structures frequently underlies adaptive change in morphology in evolution and maybe a common mechanism underlying selection. However, the mechanism by which growth is integrated within tissues during development to achieve proper proportionality is poorly understood. We have shown that signaling by potassium channels mediates coordinated size regulation in zebrafish fins. Recently, calcineurin inhibitors were shown to elicit changes in zebrafish fin allometry as well. Here, we identify the potassium channel kcnk5b as a key player in integrating calcineurin’s growth effects, in part through regulation of the cytoplasmic C-terminus of the channel. We propose that the interaction between Kcnk5b and calcineurin acts as a signaling node to regulate allometric growth. Importantly, we find that this regulation is epistatic to inherent mechanisms instructing overall size as inhibition of calcineurin is able to bypass genetic instruction of size as seen in sof and wild-type fins, however, it is not sufficient to re-specify positional memory of size of the fin. These findings integrate classic signaling mediators such as calcineurin with ion channel function in the regulation of size and proportion during growth.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted February 01, 2018.
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Bioelectric-calcineurin signaling module regulates allometric growth and size of the zebrafish fin
Jacob M Daane, Jennifer Lanni, Ina Rothenberg, Guiscard Seebohm, Charles W Higdon, Stephen L Johnson, Matthew P Harris
bioRxiv 258442; doi: https://doi.org/10.1101/258442
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Bioelectric-calcineurin signaling module regulates allometric growth and size of the zebrafish fin
Jacob M Daane, Jennifer Lanni, Ina Rothenberg, Guiscard Seebohm, Charles W Higdon, Stephen L Johnson, Matthew P Harris
bioRxiv 258442; doi: https://doi.org/10.1101/258442

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