PUBLICATION

The scale of zebrafish pectoral fin buds is determined by intercellular K+ levels and consequent Ca2+-mediated signaling via retinoic acid regulation of Rcan2 and Kcnk5b

Authors
Jiang, X., Zhao, K., Sun, Y., Song, X., Yi, C., Xiong, T., Wang, S., Yu, Y., Chen, X., Liu, R., Yan, X., Antos, C.L.
ID
ZDB-PUB-240326-3
Date
2024
Source
PLoS Biology   22: e3002565e3002565 (Journal)
Registered Authors
Antos, Christopher
Keywords
none
MeSH Terms
  • Zebrafish*/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Gene Expression Regulation, Developmental
  • Animals
  • Calcium*/metabolism
  • Animal Fins/metabolism
  • Tretinoin
(all 8)
PubMed
38527087 Full text @ PLoS Biol.
Abstract
K+ channels regulate morphogens to scale adult fins, but little is known about what regulates the channels and how they control morphogen expression. Using the zebrafish pectoral fin bud as a model for early vertebrate fin/limb development, we found that K+ channels also scale this anatomical structure, and we determined how one K+-leak channel, Kcnk5b, integrates into its developmental program. From FLIM measurements of a FRET-based K+ sensor, we observed coordinated decreases in intracellular K+ levels during bud growth, and overexpression of K+-leak channels in vivo coordinately increased bud proportions. Retinoic acid, which can enhance fin/limb bud growth, decreased K+ in bud tissues and up-regulated regulator of calcineurin (rcan2). rcan2 overexpression increased bud growth and decreased K+, while CRISPR-Cas9 targeting of rcan2 decreased growth and increased K+. We observed similar results in the adult caudal fins. Moreover, CRISPR targeting of Kcnk5b revealed that Rcan2-mediated growth was dependent on the Kcnk5b. We also found that Kcnk5b enhanced depolarization in fin bud cells via Na+ channels and that this enhanced depolarization was required for Kcnk5b-enhanced growth. Lastly, Kcnk5b-induced shha transcription and bud growth required IP3R-mediated Ca2+ release and CaMKK activity. Thus, we provide a mechanism for how retinoic acid via rcan2 can regulate K+-channel activity to scale a vertebrate appendage via intercellular Ca2+ signaling.
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Citation
Jiang, X., Zhao, K., Sun, Y., Song, X., Yi, C., Xiong, T., Wang, S., Yu, Y., Chen, X., Liu, R., Yan, X., Antos, C.L. (2024) The scale of zebrafish pectoral fin buds is determined by intercellular K+ levels and consequent Ca2+-mediated signaling via retinoic acid regulation of Rcan2 and Kcnk5b. PLoS Biology. 22:e3002565e3002565.