PUBLICATION
Maintenance of Melanocyte Stem Cell Quiescence by GABA-A Signaling in Larval Zebrafish
- Authors
- Allen, J.R., Skeath, J.B., Johnson, S.L.
- ID
- ZDB-PUB-190826-13
- Date
- 2019
- Source
- Genetics 213(2): 555-566 (Journal)
- Registered Authors
- Johnson, Stephen L.
- Keywords
- CRISPR, GABA, GABA-A receptors, inhibition, melanocyte, pigmentation, quiescence, zebrafish
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Cell Division/genetics
- Larva/genetics*
- Larva/growth & development
- Melanocytes/metabolism*
- Pigmentation/genetics
- Receptors, GABA-A/genetics*
- Regeneration/genetics
- Signal Transduction/genetics
- Stem Cells/metabolism
- Zebrafish/genetics*
- Zebrafish/growth & development
- gamma-Aminobutyric Acid/genetics
- PubMed
- 31444245 Full text @ Genetics
Citation
Allen, J.R., Skeath, J.B., Johnson, S.L. (2019) Maintenance of Melanocyte Stem Cell Quiescence by GABA-A Signaling in Larval Zebrafish. Genetics. 213(2):555-566.
Abstract
In larval zebrafish, melanocyte stem cells (MSCs) are quiescent, but can be recruited to regenerate the larval pigment pattern following melanocyte ablation. Through pharmacological experiments, we found that inhibition of GABA-A receptor function, specifically the GABA-A rho subtype, induces excessive melanocyte production in larval zebrafish. Conversely, pharmacological activation of GABA-A inhibited melanocyte regeneration. We used CRISPR-Cas9 to generate two mutant alleles of gabrr1, a subtype of GABA-A receptors. Both alleles exhibited robust melanocyte overproduction, while conditional overexpression of gabrr1 inhibited larval melanocyte regeneration. Our data suggest that gabrr1 signaling is necessary to maintain MSC quiescence and sufficient to reduce, but not eliminate, melanocyte regeneration in larval zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping