Integrated K+ channel and K+Cl- cotransporter functions are required for the coordination of size and proportion during development

• Published in: Developmental biology Vol. 456; no. 2; pp. 164 - 178
• Main Authors: Lanni, Jennifer S., Peal, David, Ekstrom, Laura, Chen, Haining, Stanclift, Caroline, Bowen, Margot E., Mercado, Adriana, Gamba, Gerardo, Kahle, Kristopher T., Harris, Matthew P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.12.2019
• Subjects: Animal Fins - growth & development; Animal Fins - metabolism; Animals; Cell Size; Female; K Cl- Cotransporters; Male; Mutation - genetics; Organ Size - physiology; Potassium Channels, Voltage-Gated - metabolism; Potassium Chloride - metabolism; Regeneration; Signal Transduction - genetics; Symporters - metabolism; Zebrafish - genetics; Zebrafish Proteins - genetics
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2019.08.016

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. Creation of dominant negative Kcc4a in wild-type fish leads to 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. [Display omitted] Highlights, Lanni et al. KCC4a.•A new zebrafish mutant shows dramatic fin overgrowth and alterations in pigment pattern•Cloning of the mutation reveals that it inactivates a potassium-chloride transport protein•Loss of ion transport causes unusual fin vasculature and dose-dependent changes in fin size•Bioelectrical input from two ion transport proteins is integrated to regulate fin growth