Integrated analysis of bioelectric signaling in regulation of proportion.

Abstract

We are proportionate entities: the mechanical and physiological function of our bodies is dependent on allometric scaling between tissues and organs. How such scaling is genetically and developmentally regulated remains a long lasting question and requires knowledge at many levels and across disciplines. Using unbiased forward genetic screens in the zebrafish, we identify mutations in potassium channels that lead to increase in relative fin size. We assess how these mutations affect electrophysiological properties of the encoded potassium channels in Xenopus oocytes. Using the zebrafish fin as an experimental platform we detail key regulation of bioelectric signaling and its control of coordinated growth during development and regeneration. Complementing these experimental approaches, we extend our investigation through a broad scale phylogenomic analysis capitalizing on natural variation in fin length in evolution as well in clinical cases of coordinated overgrowth of extremities. The combination of approaches provides mechanistic insight into bioelectric regulation of coordinated growth during development and regeneration and the prevalence of bioelectric signaling in regulating form.Support or Funding InformationNIH R01HD084985