Abstract
The scaling relationship between the size of an appendage or organ and that of the body as a whole is tightly regulated during animal development. If a structure grows at a different rate than the rest of the body, this process is termed allometric growth. The zebrafish another longfin (alf) mutant shows allometric growth resulting in proportionally enlarged fins and barbels. We took advantage of this mutant to study the regulation of size in vertebrates. Here, we show that alf mutants carry gain-of-function mutations in kcnk5b, a gene encoding a two-pore domain potassium (K+) channel. Electrophysiological analysis in Xenopus oocytes reveals that these mutations cause an increase in K+ conductance of the channel and lead to hyperpolarization of the cell. Further, somatic transgenesis experiments indicate that kcnk5b acts locally within the mesenchyme of fins and barbels to specify appendage size. Finally, we show that the channel requires the ability to conduct K+ ions to increase the size of these structures. Our results provide evidence for a role of bioelectric signaling through K+ channels in the regulation of allometric scaling and coordination of growth in the zebrafish.
Highlights
Organ growth is a complex process that requires attaining a certain shape and an appropriate size
Our analysis indicates that mutant Kcnk5b acts locally within the mesenchyme of fins and barbels to increase appendage size
In about 40% of the fish injected with plasmids encoding wild type or mutant kcnk5b and showing DsRed positive cells in the fins we found a local overgrowth phenotype (Figure 6B and H)
Summary
Organ growth is a complex process that requires attaining a certain shape and an appropriate size. Crosses between alf dt30mh and a dominant sof allele, sof dj7e2, showed no epistatic interaction between the two genes (Figure 1E), suggesting that the two mutations most likely affect independent processes that both contribute to the determination of final appendage size during fin development. To assess whether kcnk5b acts locally within fins and barbels to control growth, we transplanted kcnk5bdt30mh/+ mutant cells into wild type hosts (Figure S2A). In about 40% of the fish injected with plasmids encoding wild type or mutant kcnk5b and showing DsRed positive cells in the fins we found a local overgrowth phenotype (Figure 6B and H). No overgrowth was detected in these fish (Figure 6H), fins containing DsRed positive tissue (n = 32), including fibroblasts (Figure 6J, inset), were found These data indicate that the increase in conductance of the Kcnk5b channel is essential for the coordinated overgrowth of the fins and barbels in the mutants
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