Fate plasticity and reprogramming in genetically distinct populations of Danio leucophores

Lewis, Victor M.; Saunders, Lauren M.; Larson, Tracy A.; Bain, Emily J.; Sturiale, Samantha L.; Gur, Dvir; Chowdhury, Sarwat; Flynn, Jessica D.; Allen, Michael C.; Deheyn, Dimitri D.; Lee, Jennifer C.; Simon, Julian A.; Lippincott-Schwartz, Jennifer; Raible, David W.; Parichy, David M.

doi:10.1073/pnas.1901021116

Cited by 69melanin and skin pigmentationZebrafish Biomedical Research ApplicationsDevelopmental Biology and Gene Regulation

Fate plasticity and reprogramming in genetically distinct populations of Danio leucophores

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Lewis, Victor M., Saunders, Lauren M., Larson, Tracy A., Bain, Emily J., Sturiale, Samantha L., Gur, Dvir, Chowdhury, Sarwat, Flynn, Jessica D. +7 more·2019·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1901021116PMC PMC6575160

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Abstract

Understanding genetic and cellular bases of adult form remains a fundamental goal at the intersection of developmental and evolutionary biology. The skin pigment cells of vertebrates, derived from embryonic neural crest, are a useful system for elucidating mechanisms of fate specification, pattern formation, and how particular phenotypes impact organismal behavior and ecology. In a survey of Danio fishes, including the zebrafish Danio rerio , we identified two populations of white pigment cells—leucophores—one of which arises by transdifferentiation of adult melanophores and another of which develops from a yellow–orange xanthophore or xanthophore-like progenitor. Single-cell transcriptomic, mutational, chemical, and ultrastructural analyses of zebrafish leucophores revealed cell-type–specific chemical compositions, organelle configurations, and genetic requirements. At the organismal level, we identified distinct physiological responses of leucophores during environmental background matching, and we showed that leucophore complement influences behavior. Together, our studies reveal independently arisen pigment cell types and mechanisms of fate acquisition in zebrafish and illustrate how concerted analyses across hierarchical levels can provide insights into phenotypes and their evolution.

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pnp4a encodes a purine nucleoside phosphorylase of the purine salvage pathway expressed in both iridophores and ML.
“pnp4a, which encodes a purine nucleoside phosphorylase of the purine salvage pathway expressed in both cell types (9).”
From Agouti and BMP signaling drive a naturally occurring fate conversion of melanophores to leucophores in zebrafish (2025) · cites this paper as [9]
The Results section, “Dual Classes and Origins of Leucophores in Danio” (page unavailable), identifies pnp4a as purine nucleoside phosphorylase 4a, reports its strong expression in iridophores, and says melanoleucophores expressed a pnp4a reporter. The paper does not identify pnp4a as part of the purine salvage pathway; its discussion of purine-synthesis genes concerns de novo synthesis. (LLM, conf=0.86)
Experimental — accuracy not yet measured
In zebrafish, white highlights on fins arise through the transformation of black pigment cells into white ones.
“yet the white highlights on their fins arise differently—through the transformation of black pigment cells into white ones”
From Agouti and BMP signaling drive a naturally occurring fate conversion of melanophores to leucophores in zebrafish (2025) · cites this paper as [9]
Melanoleucophores arise from melanophores that lose their melanin over just a few days while acquiring crystalline deposits of guanine.
“Remarkably, these cells arise from melanophores that lose their melanin over just a few days while acquiring crystalline deposits of guanine.”
From Agouti and BMP signaling drive a naturally occurring fate conversion of melanophores to leucophores in zebrafish (2025) · cites this paper as [9]
Trajectory analyses bridged states in pseudotime and represented an inferred pathway of differentiation concordant with previous fate mapping in vivo.
“with trajectory analyses bridging states in pseudotime and representing an inferred pathway of differentiation concordant with previous fate mapping in vivo (Fig. 1I and SI Appendix, Fig. S4 A–F and Datasets S2–S4) (9).”
From Agouti and BMP signaling drive a naturally occurring fate conversion of melanophores to leucophores in zebrafish (2025) · cites this paper as [9]
ML contain crystals of β-guanine.
“ML contain crystals of β-guanine (9) (SI Appendix, Fig. S1E and Dataset S1).”
From Agouti and BMP signaling drive a naturally occurring fate conversion of melanophores to leucophores in zebrafish (2025) · cites this paper as [9]

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Adult cell plasticity in vivo: de-differentiation and transdifferentiation are back in style
Merrell, A. J., & Stanger, B. Z. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.24 · Cited by 369 · see citing works
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Saunders, L. M., Mishra, A. K., Aman, A. J., Lewis, V. M., Toomey, M. B., Packer, J. S., Qiu, X., McFaline-Figueroa, J. L., Corbo, J. C., Trapnell, C., et al. (2019) · eLife · doi:10.7554/elife.45181 · Cited by 170 · see citing works
Self-citation
A systems biology approach uncovers the core gene regulatory network governing iridophore fate choice from the neural crest
Petratou, K., Subkhankulova, T., Lister, J. A., Rocco, A., Schwetlick, H., & Kelsh, R. N. (2018) · PLOS Genetics · doi:10.1371/journal.pgen.1007402 · Cited by 69 · see citing works

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Sorted by citations

Thyroid hormone regulates distinct paths to maturation in pigment cell lineages
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Authors: Lewis, V. M., Saunders, L. M., Larson, T. A., Bain, E. J., Sturiale, S. L., Gur, D., Chowdhury, S., Flynn, J. D., Allen, M. C., Deheyn, D. D., Lee, J. C., Simon, J. A., Lippincott-Schwartz, J., Raible, D. W., & Parichy, D. M.
Affiliations: University of Washington (US)
University of Virginia (US)
National Institutes of Health (US)
Fred Hutch Cancer Center (US)
Scripps Institution of Oceanography (US)
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147;
Corresponding author: Parichy, David M.
ORCID: Lewis, Victor M.
Saunders, Lauren M.
Larson, Tracy A.
Bain, Emily J.
Sturiale, Samantha L.
Gur, Dvir
Chowdhury, Sarwat
Flynn, Jessica D.
Allen, Michael C.
Deheyn, Dimitri D.
Lee, Jennifer C.
Simon, Julian A.
Raible, David W.
Parichy, David M.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2019-05-28
Volume: 116
Issue: 24
Pages: 11806-11811
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1901021116
PMC: PMC6575160
OpenAlex: W2951370628
Cited by: 69
References: 3
Citations by year: 2026: 8 · 2025: 11 · 2024: 8 · 2023: 11 · 2022: 3 · 2021: 16 · 2020: 7 · 2019: 4 · 2018: 1
FWCI: 3.94
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: HHS | NIH | National Institute of General Medical Sciences (NIH R35 GM122471)
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: leucophores, zebrafish, xanthophores, neural crest, cell fate specification, background matching, single-cell transcriptomics, organelle ultrastructure, mutation analysis
MeSH terms: Cell Plasticity, Animals, Embryo, Nonmammalian, Genetics, Population, Melanophores, Mutation, Neural Crest, Phenotype, Pigmentation, Zebrafish, Gene Expression Regulation, Developmental, Transcriptome

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Fate plasticity and reprogramming in genetically distinct populations of Danio leucophores

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