Loss‐of‐function mutations in the melanocortin 1 receptor cause disruption of dorso‐ventral countershading in teleost fish
Open accessAbstract
The melanocortin 1 receptor (MC1R) is the central melanocortin receptor involved in vertebrate pigmentation. Mutations in this gene cause variations in coat coloration in amniotes. Additionally, in mammals MC1R is the main receptor for agouti‐signaling protein (ASIP), making it the critical receptor for the establishment of dorsal‐ventral countershading. In fish, Mc1r is also involved in pigmentation, but it has been almost exclusively studied in relation to melanosome dispersion activity and as a putative genetic factor involved in dark/light adaptation. However, its role as the crucial component for the Asip1‐dependent control of dorsal‐ventral pigmentation remains unexplored. Using CRISPR/Cas9, we created mc1r homozygous knockout zebrafish and found that loss‐of‐function of mc1r causes a reduction of countershading and a general paling of the animals. We find ectopic development of melanophores and xanthophores, accompanied by a decrease in iridophore numbers in the ventral region of mc1r mutants. We also reveal subtle differences in the role of mc1r in repressing pigment cell development between the skin and scale niches in ventral regions.
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Asip1 and the orthologous protein of mammals, Asip, are Melanocortin-1 receptor (Mc1r) antagonists and their ventral expression inhibits differentiation of melanophores and melanocytes, respectively, resulting in light bellies.
“Asip1 and the orthologous protein of mammals, Asip, are Melanocortin-1 receptor (Mc1r) antagonists and their ventral expression inhibits differentiation of melanophores and melanocytes, respectively, resulting in light bellies (24–27).”
From Agouti and BMP signaling drive a naturally occurring fate conversion of melanophores to leucophores in zebrafish (2025) · cites this paper as [27]
The available passages are bibliographic metadata and keywords under the Abstract label, not substantive text about Asip1 or Asip. Searches for MC1R antagonism, ventral expression, and melanophore or melanocyte differentiation found no passage establishing the claimed mechanism. (LLM, conf=0.70)
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Gross, J. B., Borowsky, R., & Tabin, C. J. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000326 · Cited by 299 · see citing works
Adaptive evolution of multiple traits through multiple mutations at a single gene
Linnen, C. R., Poh, Y.-P., Peterson, B. K., Barrett, R. D. H., Larson, J. G., Jensen, J. D., & Hoekstra, H. E. (2013) · Science · doi:10.1126/science.1233213 · Cited by 292 · see citing works
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Huang, D., Kapadia, E. H., Liang, Y., Shriver, L. P., Dai, S., Patti, G. J., Humbel, B. M., Laudet, V., & Parichy, D. M. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2424180122 · Cited by 15 · see citing works
- Authors
- Cal, L., Suarez‐Bregua, P., Braasch, I., Irion, U., Kelsh, R., Cerdá‐Reverter, J. M., & Rotllant, J.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Department of Biotechnology & Aquaculture, FishBioTech Lab. Institute of Marine Research (IIM‐CSIC) Vigo Spain
- Michigan State University (US)
- Max Planck Institute for Developmental Biology (DE)
- University of Bath (GB)
- Department of Fish Physiology and Biotechnology Institute of Aquaculture from Torre la Sal (IATS‐CSIC) Castellon Spain
- Corresponding author
- Rotllant, Josep
- Venue
- Pigment Cell & Melanoma Research
- Publisher
- Wiley
- Published
- 2019-07-12
- Volume
- 32
- Issue
- 6
- Pages
- 817-828
- ISSN
- 1755-1471 (ISSN-L)
- 1755-148X
- OpenAlex
- W2955647443
- Cited by
- 42
- References
- 2
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 7 · 2023: 8 · 2022: 11 · 2021: 6 · 2020: 3 · 2019: 1
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Pigment Cell & Melanoma Research (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Pure (University of Bath) (submittedVersion, other-oa)
- Funders
- Universidade de Vigo
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- MC1R, loss-of-function mutations, ASIP, zebrafish, melanophores, xanthophores, iridophores, skin pigmentation, pigment cell development, CRISPR/Cas9 knockout
- MeSH terms
- Loss of Function Mutation, Amino Acid Sequence, Animals, Melanophores, Models, Biological, Phenotype, Pigmentation, Zebrafish, Body Patterning, Zebrafish Proteins, Animals, Genetically Modified, Receptor, Melanocortin, Type 1, CRISPR-Cas Systems
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