PT - JOURNAL ARTICLE AU - Scott Stewart AU - Heather K. Le Bleu AU - Gabriel A. Yette AU - Astra L. Henner AU - Joshua A. Braunstein AU - Kryn Stankunas TI - <em>longfin</em> causes <em>cis</em>-ectopic expression of the <em>kcnh2a ether-a-go-go</em> K<sup>+</sup> channel to autonomously prolong fin outgrowth AID - 10.1101/790329 DP - 2019 Jan 01 TA - bioRxiv PG - 790329 4099 - http://biorxiv.org/content/early/2019/10/02/790329.short 4100 - http://biorxiv.org/content/early/2019/10/02/790329.full AB - Organs stop growing to achieve the size and shape characteristic of the species and in scale with the animal’s body. Likewise, regenerating organs sense injury extents to instruct appropriate replacement growth. Fish fins exemplify both phenomena through their tremendous diversity of form and remarkably robust regeneration. The classic zebrafish mutant longfin develops and regenerates dramatically elongated fins and underlying bony ray skeleton. We recently showed longfin disrupts the orderly depletion of a growth-promoting blastema “niche” sub-population during fin regeneration. Initial niche sizes correlate with the amount of niche-generating intra-ray mesenchyme released from variably sized and tapered rays upon injury. Therefore, skeletal geometry-defined positional information and niche depletion dynamics can explain robust fin size restoration. Here, we find the longfin eponymous phenotype is entirely caused by cis over-expression of kcnh2a, a voltage-gated potassium channel related to human ether-a-go-go. Temporal delivery of a small molecule inhibitor confirms Kcnh2a actively extends the fin outgrowth period. We use blastula transplantations to show longfin-expressed kcnh2a acts tissue autonomously in the intra-ray mesenchyme/niche lineage, where it is concordantly ectopically expressed. We propose membrane potential dynamics and downstream ion signaling promote niche-to-mesenchyme transitions to progressively slow outgrowth and thereby establish and restore fin size and shape.