An endogenous scaling mechanism in zebrafish appendages that controls two-pore potassium-leak channel activity to regulate morphogen and growth factor transcription.

The increase in activity of the two-pore potassium-leak channel Kcnk5b maintains allometric juvenile growth of adult zebrafish appendages. However, it remains unknown how this channel maintains allometric growth and how its bioelectric activity is regulated to scale these anatomical structures. We show the activation of Kcnk5b is sufficient to activate several development programs, including two morphogen pathways involved in tissue formation, shh and wnt signaling. We provide in vivo transplantation evidence that the activation of developmental programs is cell autonomous and Kcnk5b can induce the expression of these developmental programs in cultured mammalian cell lines. We also demonstrate how post-translational modification of serine 345 in Kcnk5b by calcineurin regulates channel activity and controls these developmental programs to scale the fin. Thus, we show how an endogenous bioelectric program is regulated and promotes coordinated developmental signaling to generate and scale a vertebrate appendage.