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

doi:10.1371/journal.pbio.3002565

	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
	Xiaowen Jiang; Kun Zhao; Yi Sun; Xinyue Song; Chao Yi; Tianlong Xiong; Sen Wang; Yi Yu; Xiduo Chen; Run Liu; Xin Yan; Christopher Lee Antos
	2024-03-25
发表期刊	PLOS BIOLOGY
ISSN	1545-7885
卷号	22 页码::e3002565
发表状态	已发表
DOI	10.1371/journal.pbio.3002565
摘要	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.
关键词	Pectoral fin bud development, Kcnk5b, intracellular K+, Retinoic acid, Rcan2, Depolarization, Ca2+, Proportional growth
学科门类	医学
URL	查看原文
语种	英语
EI入藏号	National Natural Science Foundation of China grants 32070820 and 32270881
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/415574
专题	生命科学与技术学院_博士生生命科学与技术学院_PI研究组_Christopher Lee Antos组生命科学与技术学院_硕士生生命科学与技术学院_本科生
共同第一作者	Kun Zhao; Yi Sun; Tianlong Xiong
通讯作者	Xiaowen Jiang
作者单位	Shanghaitech University
第一作者单位	上海科技大学
通讯作者单位	上海科技大学
第一作者的第一单位	上海科技大学
推荐引用方式 GB/T 7714	Xiaowen Jiang,Kun Zhao,Yi Sun,et al. 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[J]. PLOS BIOLOGY,2024,22::e3002565.
APA	Xiaowen Jiang.,Kun Zhao.,Yi Sun.,Xinyue Song.,Chao Yi.,...&Christopher Lee Antos.(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,:e3002565.
MLA	Xiaowen Jiang,et al."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(2024)::e3002565.