RT Journal Article
SR Electronic
T1 Integrated K<sup>+</sup> channel and K<sup>+</sup>-Cl<sup>−</sup> cotransporter functions regulate fin proportionality in zebrafish
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 621243
DO 10.1101/621243
A1 Jennifer S. Lanni
A1 David Peal
A1 Laura Ekstrom
A1 Haining Chen
A1 Caroline Stanclift
A1 Margot Bowen
A1 Adriana Mercado
A1 Gerardo Gamba
A1 Kristopher T. Kahle
A1 Matthew P. Harris
YR 2019
UL http://biorxiv.org/content/early/2019/04/28/621243.abstract
AB The coordination of growth during development establishes proportionality within and among the different anatomic structures of organisms. Innate memory of this proportionality is preserved, as shown in the ability of regenerating structures to return to their original size. Although the regulation of this coordination is incompletely understood, mutant analyses of zebrafish with long-finned phenotypes have uncovered important roles for bioelectric signaling in modulating growth and size of the fins and barbs. To date, long-finned mutants identified are caused by hypermorphic mutations, leaving unresolved whether such signaling is required for normal development. We isolated a new zebrafish mutant, schleier, with proportional overgrowth phenotypes caused by a missense mutation and loss of function in the K+-Cl− cotransporter Kcc4a. Genetic depletion of Kcc4a in wild-type fish leads to a dose-dependent loss of growth restriction in fins and barbs, supporting a requirement for Kcc4a in regulation of proportion. Epistasis experiments suggest that Kcc4a and the two-pore potassium channel Kcnk5b both contribute to a common bioelectrical signaling response in the fin. These data suggest that an integrated bioelectric signaling pathway is required for the coordination of size and proportion during development.