Cited by 91Developmental Biology and Gene RegulationZebrafish Biomedical Research Applicationsmelanin and skin pigmentation

Pigment Cell Progenitors in Zebrafish Remain Multipotent through Metamorphosis

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Singh, Ajeet Pratap, Dinwiddie, April, Mahalwar, Prateek, Schach, Ursula, Linker, Claudia, Irion, Uwe, Nüsslein-Volhard, Christiane·2016·Developmental Cell

Abstract

The neural crest is a transient, multipotent embryonic cell population in vertebrates giving rise to diverse cell types in adults via intermediate progenitors. The in vivo cell-fate potential and lineage segregation of these postembryonic progenitors is poorly understood, and it is unknown if and when the progenitors become fate restricted. We investigate the fate restriction in the neural crest-derived stem cells and intermediate progenitors in zebrafish, which give rise to three distinct adult pigment cell types: melanophores, iridophores, and xanthophores. By inducing clones in sox10-expressing cells, we trace and quantitatively compare the pigment cell progenitors at four stages, from embryogenesis to metamorphosis. At all stages, a large fraction of the progenitors are multipotent. These multipotent progenitors have a high proliferation ability, which diminishes with fate restriction. We suggest that multipotency of the nerve-associated progenitors lasting into metamorphosis may have facilitated the evolution of adult-specific traits in vertebrates.

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Crossref · 10.1016/j.devcel.2016.06.020

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  • Marker analyses and lineage-tracing experiments support the existence of a bipotent melanocyte-iridophore (MI) precursor, the fate of which is influenced by foxd3/mitfa interaction.

    “In the absence of foxd3, iridophore numbers are reduced in a manner that is at least partially mitfa-dependent, and marker analyses and lineage-tracing experiments support the existence of a bipotent melanocyte-iridophore (MI) precursor, the fate of which is influenced by this foxd3/mitfa interaction [12, 17].”

    From The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor (2021) · cites this paper as [12]

    In “Progenitors of Adult Pigment Cells Remain Multipotent from Embryogenesis to Early Metamorphosis” (page unavailable), lineage-traced MI clones support a progenitor capable of producing both melanophores and iridophores. The cited paper does not establish that a foxd3/mitfa interaction influences that progenitor’s fate; a search of our copy for foxd3 found no such evidence. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • Singh et al. identified progenitor cells proposed to generate all 3 pigment cell types throughout embryogenesis and into adulthood.

    “In a recent single cell lineage tracing study, Singh et al., identified progenitor cells proposed to generate all 3 pigment cell types throughout embryogenesis and into adulthood.”

    From The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor (2021) · cites this paper as [12]

    The Introduction (page not supplied) says Singh et al. induced clones from embryogenesis to early metamorphosis and analyzed them in 2- to 3-month-old fish. The Discussion (page not supplied) says the progenitors generate all three pigment cell types of the adult color pattern. The study supports their multipotency through early metamorphosis, but does not show that they continue generating all three types throughout adulthood. (LLM, conf=0.87)

    Experimental — accuracy not yet measured
  • The vast majority of these progenitor cells were also able to give rise to neuronal and glial lineages.

    “However, it was shown that the vast majority of these were also able to give rise to neuronal and glial lineages [12].”

    From The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor (2021) · cites this paper as [12]

    The section “Progenitors of Adult Pigment Cells Remain Multipotent from Embryogenesis to Early Metamorphosis” reports pigment-cell clones that also labeled neurons and/or glia. The proportions were 75%, 72%, 68%, and 47% at successive activation times, so the paper does not establish that the vast majority gave rise to neural lineages at every stage, or that individual progenitors gave rise to both neurons and glia. No page number is available in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • These results strongly argue for the absence of a strictly tripotent progenitor (Cbl(late)) in each of the 3 embryonic and 1 adult stages when the studies were conducted.

    “These results strongly argue for the absence of a strictly tripotent progenitor (Cbl(late)) in each of the 3 embryonic and 1 adult stages when the studies were conducted; but the hypothesis that a transient Cbl(late) cell exists during a brief time window (between 18 hpf and 24 hpf) cannot be strictly ruled out.”

    From The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor (2021) · cites this paper as [12]

    The section “Pigment Cell Progenitors Do Not Display Stereotypic Cell-Fate Restrictions” (page not provided) says most traced cells remain multipotent and lack stereotypic restrictions, which is consistent with an argument against an obligatory strictly tripotent progenitor. It does not establish the absence of such a progenitor at every tested stage. The methods section (page not provided) also identifies the four stages as embryonic, larval, premetamorphic, and metamorphic—not three embryonic stages and one adult stage. (LLM, conf=0.84)

    Experimental — accuracy not yet measured
  • Previous analyses used a sox10:CreERt2 transgene that can mark most or all postembryonic neural crest derivatives, including multipotent progenitors in the peripheral nervous system, and cells transiting from the peripheral nervous system to the hypodermis of the skin.

    “Previous analyses used a sox10:CreERt2 transgene that can mark most or all postembryonic neural crest derivatives, including multipotent progenitors in the peripheral nervous system, and cells transiting from the peripheral nervous system to the hypodermis of the skin12,46”

    From In situ differentiation of iridophore crystallotypes underlies zebrafish stripe patterning (2020) · cites this paper as [46]

    The section on progenitors of adult pigment cells describes using Tg(sox10:ER T2-Cre) to label postembryonic neural crest-derived clones and reports multipotent progenitors that give rise to pigment and peripheral neural cells. The Introduction describes pigment-cell progenitors traveling along peripheral nerves to the skin. The paper does not establish that the transgene can mark most or all postembryonic neural crest derivatives; its analysis is limited to selected clones in the zebrafish trunk. It also does not identify the skin destination specifically as the hypodermis. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 3

  1. Kelsh, R.N., Harris, M.L., Colanesi, S., and Erickson, C.A. (2009). Stripes and belly-spots-a review of pigment cell morphogenesis in vertebrates. Semin. Cell Dev. Biol. 20, 90-104.
  2. McGraw, H.F., Snelson, C.D., Prendergast, A., Suli, A., and Raible, D.W. (2012). Postembryonic neuronal addition in zebrafish dorsal root ganglia is regulated by Notch signaling. Neural Dev. 7, 23.
  3. O'Reilly-Pol, T., and Johnson, S.L. (2009). Melanocyte regeneration reveals mechanisms of adult stem cell regulation. Semin. Cell Dev. Biol. 20, 117-124.

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Authors
Singh, A. P., Dinwiddie, A., Mahalwar, P., Schach, U., Linker, C., Irion, U., & Nüsslein-Volhard, C.
Affiliations
  • Max Planck Institute for Developmental Biology (DE)
  • King's College London (GB)
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2016-08
Volume
38
Issue
3
Pages
316-330
ISSN
1534-5807 (ISSN-L)
OpenAlex
W2486215435
Cited by
91
References
0
Citations by year
2026: 7 · 2025: 7 · 2024: 6 · 2023: 10 · 2022: 5 · 2021: 19 · 2020: 8 · 2019: 12 · 2018: 10 · 2017: 5 · 2016: 2
FWCI
4.13
Type
journal article
Language
en
Open access
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
Max Planck Society
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
Keywords
neural crest, multipotency, metamorphosis, melanophores, iridophores, xanthophores, SOX10, lineage tracing, cell proliferation, zebrafish, intermediate progenitor cells
MeSH terms
Animals, Cell Differentiation, Embryo, Nonmammalian, Biological Evolution, Melanophores, Metamorphosis, Biological, Neural Crest, Phenotype, Pigmentation, Zebrafish, Gene Expression Regulation, Developmental, Cell Lineage, Multipotent Stem Cells, Embryonic Development

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