longfincausescis-ectopic expression of thekcnh2a ether-a-go-goK⁺channel to autonomously prolong fin outgrowth

Abstract

40Organs 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 45 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-50 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 55 niche-to-mesenchyme transitions to progressively slow outgrowth and thereby establish and restore fin size and shape.

Evolution of the potassium channel geneKcnj13underlies colour pattern diversification inDaniofish

“…Potassium channels have important roles in tissue patterning 51 , notably in the regulation of allometric growth of fins in D. rerio 52,53 . Kcnj13 encodes an inwardly rectifying potassium channel (Kir7.1) conserved in vertebrates (Extended Data Fig.…”

Skeletal geometry and niche transitions restore organ size and shape during zebrafish fin regeneration

“…As such, we provide a framework to understand evolutionary origins of appendage size and shape variation. In the accompanying manuscript, we identify cis ectopic expression of the voltage-gated potassium channel kcnh2a in mesenchyme/niche lineage as the long sought cause of longfin t2 (Stewart et al, 2019). These studies link ion signaling or bioelectricity, widely connected to organ size control and regeneration (McLaughlin and Levin,285 2018), to gene regulatory pathways regulating cell state transitions that slow then terminate fin outgrowth.…”

The developmental and genetic architecture of the sexually selected male ornament of swordtails

“…In zebrafish long fin mutants, mutations in several potassium channel genes, including kcnh2a, kcnk5b, and kcc4a cause various types of fin overgrowth [49][50][51]. In fighting fish, Betta splendens, kcnh8 misexpression is associated with pectoral fin overgrowth (Wang et al submitted).…”