PUBLICATION

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

Authors
Lanni, J.S., Peal, D., Ekstrom, L., Chen, H., Stanclift, C., Bowen, M.E., Mercado, A., Gamba, G., Kahle, K.T., Harris, M.P.
ID
ZDB-PUB-190902-23
Date
2019
Source
Developmental Biology   456(2): 164-178 (Journal)
Registered Authors
Harris, Matthew
Keywords
none
MeSH Terms
  • Animal Fins/growth & development*
  • Animal Fins/metabolism
  • Animals
  • Cell Size
  • Female
  • 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
PubMed
31472116 Full text @ Dev. Biol.
Abstract
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.
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Mutations / Transgenics
Human Disease / Model
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Mapping