PUBLICATION

Potassium Channel-Associated Bioelectricity of the Dermomyotome Determines Fin Patterning in Zebrafish

Authors
Silic, M.R., Wu, Q., Kim, B.H., Golling, G., Chen, K.H., Freitas, R., Chubykin, A.A., Mittal, S.K., Zhang, G.
ID
ZDB-PUB-200618-4
Date
2020
Source
Genetics   215(4): 1067-1084 (Journal)
Registered Authors
Freitas, Renata, Golling, Greg, Zhang, GuangJun
Keywords
CRISPR, Potassium channel, bioelectricity, dermomyotome, kcnj13/kir7.1, long fin, patterning, somite, zebrafish
MeSH Terms
  • Animal Fins/physiology*
  • Animals
  • Animals, Genetically Modified/physiology*
  • Bioelectric Energy Sources
  • Body Patterning*
  • Electricity*
  • Epithelial Cells/metabolism
  • Gene Expression Regulation*
  • Muscles/metabolism
  • Potassium Channels/genetics
  • Potassium Channels/metabolism*
  • Somites/metabolism
  • Zebrafish/physiology*
PubMed
32546498 Full text @ Genetics
Abstract
The roles of bioelectric signaling in developmental patterning remain largely unknown, although recent work has implicated bioelectric signals in cellular processes such as proliferation and migration. Here, we report a mutation in the inwardly rectifying potassium channel (kir) gene, kcnj13/kir7.1, that causes elongation of the fins in the zebrafish insertional mutant Dhi2059. A viral DNA insertion into the noncoding region of kcnj13 results in transient activation and ectopic expression of kcnj13 in the dermomyotome, from which the fin ray progenitors originate. We made an allele-specific loss-of-function kcnj13 CRISPR mutant and showed that it could reverse the long-finned phenotype, but only when located on the same chromosome as the Dhi2059 viral insertion. Also, we showed that ectopic expression of kcnj13 in the dermomyotome of transgenic zebrafish produces phenocopies of the Dhi2059 mutant in a gene dosage-sensitive manner. Finally, to determine whether this developmental function is specific to kcnj13, we ectopically expressed three additional potassium channel genes, kcnj1b, kcnj10a, and kcnk9 We found that all induce the long-finned phenotype, indicating that this function is conserved among potassium channel genes. Taken together, our results suggest that dermomyotome bioelectricity is a new fin patterning mechanism, and we propose a two-stage bioelectricity model for zebrafish fin patterning. This ion-channel-regulated bioelectric developmental patterning mechanism may provide us new insight into vertebrate morphological evolution and human congenital malformations.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping