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Cited by 67melanin and skin pigmentationZebrafish Biomedical Research ApplicationsDevelopmental Biology and Gene Regulation

Countershading in zebrafish results from an Asip1 controlled dorsoventral gradient of pigment cell differentiation

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Cal, Laura, Suarez-Bregua, Paula, Comesaña, Pilar, Owen, Jennifer, Braasch, Ingo, Kelsh, Robert, Cerdá-Reverter, José Miguel, Rotllant, Josep·2019·Scientific Reports
DOI 10.1038/s41598-019-40251-zPMC PMC6401153
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Abstract

Dorso-ventral (DV) countershading is a highly-conserved pigmentary adaptation in vertebrates. In mammals, spatially regulated expression of agouti-signaling protein (ASIP) generates the difference in shading by driving a switch between the production of chemically-distinct melanins in melanocytes in dorsal and ventral regions. In contrast, fish countershading seemed to result from a patterned DV distribution of differently-coloured cell-types (chromatophores). Despite the cellular differences in the basis for counter-shading, previous observations suggested that Agouti signaling likely played a role in this patterning process in fish. To test the hypotheses that Agouti regulated counter-shading in fish, and that this depended upon spatial regulation of the numbers of each chromatophore type, we engineered asip1 homozygous knockout mutant zebrafish. We show that loss-of-function asip1 mutants lose DV countershading, and that this results from changed numbers of multiple pigment cell-types in the skin and on scales. Our findings identify asip1 as key in the establishment of DV countershading in fish, but show that the cellular mechanism for translating a conserved signaling gradient into a conserved pigmentary phenotype has been radically altered in the course of evolution.

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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 [26]

    The Discussion supports the zebrafish portion: it reports that Asip1 binds Mc1r as an antagonist and represses ventral melanophore differentiation. But the Introduction and Discussion describe mammalian ASIP as changing the type of melanin produced by melanocytes, not inhibiting melanocyte differentiation. The claimed mechanism for mammalian light bellies is therefore not supported. (LLM, conf=0.90)

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Authors
Cal, L., Suarez-Bregua, P., Comesaña, P., Owen, J., Braasch, I., Kelsh, R., Cerdá-Reverter, J. M., & Rotllant, J.
Affiliations
  • Consejo Superior de Investigaciones Científicas (ES)
  • University of Bath (GB)
  • Michigan State University (US)
Corresponding author
Rotllant, Josep
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2019-03-05
Volume
9
Issue
1
Pages
3449-3449
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-019-40251-z
PMC
PMC6401153
OpenAlex
W2920588547
Cited by
67
References
1
Citations by year
2026: 6 · 2025: 7 · 2024: 12 · 2023: 13 · 2022: 3 · 2021: 10 · 2020: 9 · 2019: 7
FWCI
3.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure (University of Bath) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Ministerio de Economía y Competitividad (AGL2011-23581, AGL2014-52473R, AGL2017-89648P)
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
countershading, dorsoventral patterning, zebrafish, pigment cell differentiation, chromatophores, melanocytes, melanin, scale, skin pigmentation, loss-of-function mutants
MeSH terms
Loss of Function Mutation, Amino Acid Sequence, Animals, Cell Differentiation, Phenotype, Pigmentation, Zebrafish, Gene Targeting, Body Patterning, Agouti Signaling Protein, Genetic Loci, CRISPR-Cas Systems

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