Overexpression of potassium channel Kcna5 alters skeletal patterning in the zebrafish regenerating fin

Skeletal patterning relies on a complex network of molecular and genetic regulators. However, our understanding of pathways governing joint placement and morphogenesis remains incomplete. Prior studies have demonstrated that medially located Cx43 mediated gap junctional intercellular communication (GJIC) inhibits joint formation by the adjacent lateral skeletal precursor cells, and thereby determines skeletal patterning in the teleost regenerating fin. Here, we test the model that Cx43-GJIC regulates joint formation by propagating changes in membrane potential (ΔV_m). To provide evidence that ΔV_m is sufficient to influence joint formation, we generated a transgenic line that expresses the X. laevis voltage-gated channel, shaker-related subfamily, member 5 (kcna5) behind the temperature-inducible heat shock protein 70 (hsp70) promoter. Using this line, we demonstrate that Xl-kcna5 overexpression delays evx1 expression and causes longer segments. Moreover, the increased segment length in response to Xl-Kcna5 overexpression requires Cx43. These findings support a model whereby potassium channels act together with gap junction channels to influence joint formation, and therefore skeletal patterning, in the zebrafish regenerating fin.