Cited by 216melanin and skin pigmentationZebrafish Biomedical Research ApplicationsDevelopmental Biology and Gene Regulation

Iridophores and their interactions with other chromatophores are required for stripe formation in zebrafish

Open access
Frohnhöfer, Hans Georg, Krauss, Jana, Maischein, Hans-Martin, Nüsslein-Volhard, Christiane·2013·Development

Abstract

Colour patterns of adult fish are produced by several types of pigment cells that distribute in the dermis during juvenile development. The zebrafish, Danio rerio, displays a striking pattern of dark stripes of melanophores interspersed by light stripes of xanthophores. Mutants lacking either cell type do not form proper stripes, indicating that interactions between these two chromatophore types are required for stripe formation. A third cell type, silvery iridophores, participates to render a shiny appearance to the pattern, but its role in stripe formation has been unclear. Mutations in rose (rse) or shady (shd) cause a lack or strong reduction of iridophores in adult fish; in addition, the melanophore number is drastically reduced and stripes are broken up into spots. We show that rse and shd are autonomously required in iridophores, as mutant melanophores form normal sized stripes when confronted with wild-type iridophores in chimeric animals. We describe stripe formation in mutants missing one or two of the three chromatophore types. None of the chromatophore types alone is able to create a pattern but residual stripe formation occurs with two cell types. Our analysis shows that iridophores promote and sustain melanophores. Furthermore, iridophores attract xanthophores, whereas xanthophores repel melanophores. We present a model for the interactions between the three chromatophore types underlying stripe formation. Stripe formation is initiated by iridophores appearing at the horizontal myoseptum, which serves as a morphological landmark for stripe orientation, but is subsequently a self-organising process.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1242/dev.096719

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Stromal cells of the hypodermis and iridophores regulate melanophore and xanthophore numbers during adult pigment pattern formation.

    “stromal cells of the hypodermis (Lang et al., 2009) and also iridophores (Frohnhöfer et al., 2013; Patterson and Parichy, 2013) regulate melanophore and xanthophore numbers during adult pigment pattern formation”

    From Thyroid hormone regulates distinct paths to maturation in pigment cell lineages (2019) · cites this paper as Frohnhöfer et al., 2013

    The Results section, “Development of the adult pattern in iridophore mutants” (page unavailable), reports markedly fewer melanophores in mutants with reduced or absent iridophores. It describes delayed xanthophore appearance and altered distribution, but does not establish that iridophores regulate xanthophore numbers. The stromal-cell part of the sentence is attributed to a different citation and is not judged here. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Genetically or experimentally induced deficiencies in iridophores cause pattern defects, including alterations in primary stripe positioning and boundary formation, and also lead to reductions or losses of secondary interstripes and stripes.

    “The iridophore’s importance in skin patterning has been demonstrated in experiments showing that genetically or experimentally induced deficiencies in iridophores cause pattern defects, including alterations in primary stripe positioning and boundary formation, and also lead to reductions or losses of secondary interstripes and stripes13–17.”

    From In situ differentiation of iridophore crystallotypes underlies zebrafish stripe patterning (2020) · cites this paper as [14]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured
  • The authors' data, together with those of others, suggest that some of these signals depend on melanophores, promoting differentiation of iridoblasts toward a state having ordered reflecting crystal platelets that are physiologically responsive (blue ⟷ yellow) in stripes, and away from an alternative state of disordered-crystal platelets lacking physiological responsiveness (silvery-yellow) in the

    “Our data, together with those of others, suggest that some of these signals depend on melanophores14,15,25,47, promoting differentiation of iridoblasts toward a state having ordered reflecting crystal platelets that are physiologically responsive (blue ⟷ yellow) in stripes, and away from an alternative state of disordered-crystal platelets lacking physiological responsiveness (silvery-yellow) in”

    From In situ differentiation of iridophore crystallotypes underlies zebrafish stripe patterning (2020) · cites this paper as [14]

    The Results (‘Mutants lacking xanthophores and melanophores display abnormal iridophore distribution’; page unavailable) show altered iridophore distribution when melanophores are absent, supporting a role for melanophores in their patterning. The paper also describes blue iridophores in stripes, but it does not establish that melanophore-dependent signals direct iridoblast differentiation toward ordered, physiologically responsive crystal platelets rather than disordered, unresponsive ones. (LLM, conf=0.82)

    Experimental — accuracy not yet measured
  • Mutants for mitfa, which lack melanophores, have the dense morphology iridophores over a broader area than wild-type fish.

    “Prior work has hinted at this possibility as mutants for melanophore-inducing transcription factor (mitfa), which lack melanophores, have the dense morphology iridophores (characteristic of interstripe zones) over a broader area than wild-type fish14,27.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 39

  1. Asai R. Taguchi E. Kume Y. Saito M. Kondo S. (1999). Zebrafish leopard gene as a component of the putative reaction-diffusion system. Mech. Dev. 89, 87– 92 10559483
  2. Brand M. Granato M. Nüsslein-Volhard C. (2002). Keeping and raising zebrafish. In Zebrafish: A Practical Approach (ed. Nüsslein-Volhard C. Dahm R.), pp. 7– 37 New York, NY: Oxford University Press
  3. Budi E. H. Patterson L. B. Parichy D. M. (2008). Embryonic requirements for ErbB signaling in neural crest development and adult pigment pattern formation. Development 135, 2603– 2614 18508863 PMC2704560
  4. Budi E. H. Patterson L. B. Parichy D. M. (2011). Post-embryonic nerve-associated precursors to adult pigment cells: genetic requirements and dynamics of morphogenesis and differentiation. PLoS Genet. 7, e1002044 21625562 PMC3098192
  5. Dooley C. M. Mongera A. Walderich B. Nüsslein-Volhard C. (2013). On the embryonic origin of adult melanophores: the role of ErbB and Kit signalling in establishing melanophore stem cells in zebrafish. Development 140, 1003– 1013 23364329
  6. Eisen J. S. Weston J. A. (1993). Development of the neural crest in the zebrafish. Dev. Biol. 159, 50– 59 8365574
  7. Gierer A. Meinhardt H. (1972). A theory of biological pattern formation. Kybernetik 12, 30– 39 4663624
  8. Haffter P. Odenthal J. Mullins M. C. Lin S. Farrell M. J. Vogelsang E. Haas F. Brand M. van Eeden F. J. M. Furutani-Seiki M. (1996). Mutations affecting pigmentation and shape of the adult zebrafish. Dev. Genes Evol. 206, 260– 276 24173565
  9. Hirata M. Nakamura K. Kanemaru T. Shibata Y. Kondo S. (2003). Pigment cell organization in the hypodermis of zebrafish. Dev. Dyn. 227, 497– 503 12889058
  10. Hultman K. A. Johnson S. L. (2010). Differential contribution of direct-developing and stem cell-derived melanocytes to the zebrafish larval pigment pattern. Dev. Biol. 337, 425– 431 19931238 PMC2812685
  11. Hultman K. A. Budi E. H. Teasley D. C. Gottlieb A. Y. Parichy D. M. Johnson S. L. (2009). Defects in ErbB-dependent establishment of adult melanocyte stem cells reveal independent origins for embryonic and regeneration melanocytes. PLoS Genet. 5, e1000544 19578401 PMC2699538
  12. Johnson S. L. Africa D. Walker C. Weston J. A. (1995). Genetic control of adult pigment stripe development in zebrafish. Dev. Biol. 167, 27– 33 7851648
  13. Kane D. A. Kishimoto T. (2002). Cell labeling and transplantation techniques. In Zebrafish: A Practical Approach (ed. Nüsslein-Volhard C. Dahm R.), pp. 95– 119 New York, NY: Oxford University Press
  14. Kelsh R. N. (2004). Genetics and evolution of pigment patterns in fish. Pigment Cell Res. 17, 326– 336 15250934
  15. Kelsh R. N. Brand M. Jiang Y. J. Heisenberg C. P. Lin S. Haffter P. Odenthal J. Mullins M. C. van Eeden F. J. Furutani-Seiki M. (1996). Zebrafish pigmentation mutations and the processes of neural crest development. Development 123, 369– 389 9007256
  16. Kirschbaum F. (1975). Untersuchungen über das Farbmuster der Zebrabarbe Brachydanio rerio (Cyprinidae, Teleostei). Roux’s Arch. Dev. Biol. 177, 129– 152 28304951
  17. Krauss J. Astrinides P. Frohnhöfer H. G. Walderich B. Nüsslein-Volhard C. (2013). transparent, a gene affecting stripe formation in zebrafish, encodes the mitochondrial protein Mpv17 that is required for iridophore survival. Biol. Open (in press). PMC3711038 23862018
  18. Lang M. R. Patterson L. B. Gordon T. N. Johnson S. L. Parichy D. M. (2009). Basonuclin-2 requirements for zebrafish adult pigment pattern development and female fertility. PLoS Genet. 5, e1000744 19956727 PMC2776513
  19. Levesque M. P. Krauss J. Koehler C. Boden C. Harris M. P. (2013). New tools for the identification of developmentally regulated enhancer regions in embryonic and adult zebrafish. Zebrafish 10, 21– 29 23461416 PMC3670562
  20. Lister J. A. Robertson C. P. Lepage T. Johnson S. L. Raible D. W. (1999). nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate. Development 126, 3757– 3767 10433906
  21. Lopes S. S. Yang X. Müller J. Carney T. J. McAdow A. R. Rauch G. J. Jacoby A. S. Hurst L. D. Delfino-Machín M. Haffter P. (2008). Leukocyte tyrosine kinase functions in pigment cell development. PLoS Genet. 4, e1000026 18369445 PMC2265441
  22. Maderspacher F. Nüsslein-Volhard C. (2003). Formation of the adult pigment pattern in zebrafish requires leopard and obelix dependent cell interactions. Development 130, 3447– 3457 12810592
  23. Meinhardt H. Gierer A. (1980). Generation and regeneration of sequence of structures during morphogenesis. J. Theor. Biol. 85, 429– 450 7442273
  24. Nakamasu A. Takahashi G. Kanbe A. Kondo S. (2009). Interactions between zebrafish pigment cells responsible for the generation of Turing patterns. Proc. Natl. Acad. Sci. USA 106, 8429– 8434 19433782 PMC2689028
  25. Odenthal J. Rossnagel K. Haffter P. Kelsh R. N. Vogelsang E. Brand M. van Eeden F. J. Furutani-Seiki M. Granato M. Hammerschmidt M. (1996). Mutations affecting xanthophore pigmentation in the zebrafish, Danio rerio. Development 123, 391– 398 9007257
  26. Parichy D. M. Turner J. M. (2003). Temporal and cellular requirements for Fms signaling during zebrafish adult pigment pattern development. Development 130, 817– 833 12538511
  27. Parichy D. M. Rawls J. F. Pratt S. J. Whitfield T. T. Johnson S. L. (1999). Zebrafish sparse corresponds to an orthologue of c-kit and is required for the morphogenesis of a subpopulation of melanocytes, but is not essential for hematopoiesis or primordial germ cell development. Development 126, 3425– 3436 10393121
  28. Parichy D. M. Ransom D. G. Paw B. Zon L. I. Johnson S. L. (2000a). An orthologue of the kit-related gene fms is required for development of neural crest-derived xanthophores and a subpopulation of adult melanocytes in the zebrafish, Danio rerio. Development 127, 3031– 3044 10862741
  29. Parichy D. M. Mellgren E. M. Rawls J. F. Lopes S. S. Kelsh R. N. Johnson S. L. (2000b). Mutational analysis of endothelin receptor b1 (rose) during neural crest and pigment pattern development in the zebrafish Danio rerio. Dev. Biol. 227, 294– 306 11071756
  30. Parichy D. M. Elizondo M. R. Mills M. G. Gordon T. N. Engeszer R. E. (2009). Normal table of postembryonic zebrafish development: staging by externally visible anatomy of the living fish. Dev. Dyn. 238, 2975– 3015 19891001 PMC3030279
  31. Raible D. W. Eisen J. S. (1994). Restriction of neural crest cell fate in the trunk of the embryonic zebrafish. Development 120, 495– 503 8162850
  32. Svetic V. Hollway G. E. Elworthy S. Chipperfield T. R. Davison C. Adams R. J. Eisen J. S. Ingham P. W. Currie P. D. Kelsh R. N. (2007). Sdf1a patterns zebrafish melanophores and links the somite and melanophore pattern defects in choker mutants. Development 134, 1011– 1022 17267445
  33. Takahashi G. Kondo S. (2008). Melanophores in the stripes of adult zebrafish do not have the nature to gather, but disperse when they have the space to move. Pigment Cell Melanoma Res. 21, 677– 686 19067972
  34. Tryon R. C. Higdon C. W. Johnson S. L. (2011). Lineage relationship of direct-developing melanocytes and melanocyte stem cells in the zebrafish. PLoS ONE 6, e21010 21698209 PMC3116864
  35. Tu S. Johnson S. L. (2011). Fate restriction in the growing and regenerating zebrafish fin. Dev. Cell 20, 725– 732 21571228 PMC3096007
  36. Turing A. (1952). The chemical basis of morphogenesis. Philos. Trans. R. Soc. B 237, 37– 72 PMC4360114 25750229
  37. van Eeden F. J. Granato M. Schach U. Brand M. Furutani-Seiki M. Haffter P. Hammerschmidt M. Heisenberg C. P. Jiang Y. J. Kane D. A. (1996). Mutations affecting somite formation and patterning in the zebrafish, Danio rerio. Development 123, 153– 164 9007237
  38. Walker C. Streisinger G. (1983). Induction of Mutations by gamma-Rays in Pregonial Germ Cells of Zebrafish Embryos. Genetics 103, 125– 136 17246099 PMC1202017
  39. Yamaguchi M. Yoshimoto E. Kondo S. (2007). Pattern regulation in the stripe of zebrafish suggests an underlying dynamic and autonomous mechanism. Proc. Natl. Acad. Sci. USA 104, 4790– 4793 17360399 PMC1820822

Cited by

Sorted by citations

Authors
Frohnhöfer, H. G., Krauss, J., Maischein, H.-M., & Nüsslein-Volhard, C.
Affiliations
  • Max Planck Institute for Developmental Biology (DE)
  • Max-Planck-Institut für Entwicklungsbiologie, Spemannstr 35, 72076 Tübingen, Germany.
Corresponding author
Frohnhöfer, Hans Georg
Venue
Development
Published
2013-07-15
Volume
140
Issue
14
Pages
2997-3007
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
OpenAlex
W2117822539
Cited by
216
References
1
Citations by year
2026: 15 · 2025: 12 · 2024: 15 · 2023: 15 · 2022: 11 · 2021: 28 · 2020: 17 · 2019: 23 · 2018: 15 · 2017: 18 · 2016: 12 · 2015: 15 · 2014: 16 · 2013: 4
FWCI
7.22
Type
journal article
Language
en
Open access
Locations
  • Development (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
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
iridophores, melanophores, xanthophores, stripe formation, zebrafish, chimeric animals, self-organization
MeSH terms
Animals, Chromatophores, Melanophores, Models, Biological, Pigmentation, Zebrafish, Body Patterning

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review