Cited by 45melanin and skin pigmentationDevelopmental Biology and Gene RegulationZebrafish Biomedical Research Applications

Heterotypic interactions regulate cell shape and density during color pattern formation in zebrafish

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Mahalwar, Prateek, Singh, Ajeet Pratap, Fadeev, Andrey, Nüsslein-Volhard, Christiane, Irion, Uwe·2016·Biology Open

Abstract

The conspicuous striped coloration of zebrafish is produced by cell-cell interactions among three different types of chromatophores: black melanophores, orange/yellow xanthophores and silvery/blue iridophores. During color pattern formation xanthophores undergo dramatic cell shape transitions and acquire different densities, leading to compact and orange xanthophores at high density in the light stripes, and stellate, faintly pigmented xanthophores at low density in the dark stripes. Here, we investigate the mechanistic basis of these cell behaviors in vivo, and show that local, heterotypic interactions with dense iridophores regulate xanthophore cell shape transition and density. Genetic analysis reveals a cell-autonomous requirement of gap junctions composed of Cx41.8 and Cx39.4 in xanthophores for their iridophore-dependent cell shape transition and increase in density in light-stripe regions. Initial melanophore-xanthophore interactions are independent of these gap junctions; however, subsequently they are also required to induce the acquisition of stellate shapes in xanthophores of the dark stripes. In summary, we conclude that, whereas homotypic interactions regulate xanthophore coverage in the skin, their cell shape transitions and density is regulated by gap junction-mediated, heterotypic interactions with iridophores and melanophores.

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  • 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 [47]

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Research works printed but not linked: 49

  1. Anelli V., Santoriello C., Distel M., Köster R. W., Ciccarelli F. D. and Mione M. (2009). Global repression of cancer gene expression in a zebrafish model of melanoma is linked to epigenetic regulation. Zebrafish 6, 417- 424. 10.1089/zeb.2009.0612 20047469 · DOI
  2. Bertrand J. Y., Chi N. C., Santoso B., Teng S., Stainier D. Y. R. and Traver D. (2010). Haematopoietic stem cells derive directly from aortic endothelium during development. Nature 464, 108- 111. 10.1038/nature08738 20154733 PMC2858358 · DOI
  3. Brand M., Granato M. and Nüsslein-Volhard C. (2002). Keeping and raising zebrafish In Zebrafish: A Practical Approach (ed. C. Nüsslein-Volhard and R. Dahm) pp. 7-37. New York: Oxford University Press.
  4. Budi E. H., Patterson L. B. and Parichy D. M. (2008). Embryonic requirements for ErbB signaling in neural crest development and adult pigment pattern formation. Development 135, 2603- 2614. 10.1242/dev.019299 18508863 PMC2704560 · DOI · Paper page
  5. Dooley C. M., Mongera A., Walderich B. and 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. 10.1242/dev.087007 23364329 · DOI
  6. Eom D. S., Bain E. J., Patterson L. B., Grout M. E. and Parichy D. M. (2015). Long-distance communication by specialized cellular projections during pigment pattern development and evolution. eLife 4, e12401 10.7554/eLife.12401 26701906 PMC4764569 · DOI
  7. Fadeev A., Krauss J., Fröhnhofer H. G., Irion U. and Nüsslein-Volhard C. (2015). Tight junction protein 1a regulates pigment cell organisation during zebrafish colour patterning. eLife 4, 1711 10.7554/eLife.06545 PMC4446668 25915619 · DOI · Paper page
  8. Fadeev A., Krauss J., Singh A. P. and Nüsslein-Volhard C. (2016). Zebrafish Leucocyte tyrosine kinase controls iridophore establishment, proliferation and survival. Pigment Cell Melanoma Res. 29, 284- 296. 10.1111/pcmr.12454 26801003 · DOI · Paper page
  9. Fernandes A. M., Fero K., Arrenberg A. B., Bergeron S. A., Driever W. and Burgess H. A. (2012). Deep brain photoreceptors control light-seeking behavior in zebrafish larvae. Curr. Biol. 22, 2042- 2047. 10.1016/j.cub.2012.08.016 23000151 PMC3494761 · DOI
  10. Frohnhöfer H. G., Krauss J., Maischein H.-M. and Nüsslein-Volhard C. (2013). Iridophores and their interactions with other chromatophores are required for stripe formation in zebrafish. Development 140, 2997- 3007. 10.1242/dev.096719 23821036 PMC3912879 · DOI · Paper page
  11. Frohnhöfer H. G., Geiger-Rudolph S., Pattky M., Meixner M., Huhn C., Maischein H.-M., Geisler R., Gehring I., Maderspacher F., Nüsslein-Volhard C. et al. (2016). Spermidine, but not spermine, is essential for pigment pattern formation in zebrafish. Biol. Open 5, 736- 744. 10.1242/bio.018721 27215328 PMC4920196 · DOI
  12. Gray C., Loynes C. A., Whyte M. K. B., Crossman D. C., Renshaw S. A. and Chico T. J. A. (2011). Simultaneous intravital imaging of macrophage and neutrophil behaviour during inflammation using a novel transgenic zebrafish. Thromb. Haemost. 105, 811- 819. 10.1160/TH10-08-0525 21225092 · DOI
  13. Hamada H., Watanabe M., Lau H. E., Nishida T., Hasegawa T., Parichy D. M. and Kondo S. (2014). Involvement of Delta/Notch signaling in zebrafish adult pigment stripe patterning. Development 141, 318- 324. 10.1242/dev.099804 24306107 PMC3879813 · DOI
  14. Hirata M., Nakamura K., Kanemaru T., Shibata Y. and Kondo S. (2003). Pigment cell organization in the hypodermis of zebrafish. Dev. Dyn. 227, 497- 503. 10.1002/dvdy.10334 12889058 · DOI
  15. Hirata M., Nakamura K.-I. and Kondo S. (2005). Pigment cell distributions in different tissues of the zebrafish, with special reference to the striped pigment pattern. Dev. Dyn. 234, 293- 300. 10.1002/dvdy.20513 16110504 · DOI
  16. Hwang W. Y., Fu Y., Reyon D., Maeder M. L., Kaini P., Sander J. D., Joung J. K., Peterson R. T. and Yeh J.-R. J. (2013a). Heritable and precise zebrafish genome editing using a CRISPR-Cas system. PLoS ONE 8, e68708 10.1371/journal.pone.0068708 23874735 PMC3706373 · DOI
  17. Inaba M., Yamanaka H. and Kondo S. (2012). Pigment pattern formation by contact-dependent depolarization. Science 335, 677 10.1126/science.1212821 22323812 · DOI · Paper page
  18. Inoue S., Kondo S., Parichy D. M. and Watanabe M. (2014). Tetraspanin 3c requirement for pigment cell interactions and boundary formation in zebrafish adult pigment stripes. Pigment Cell Melanoma Res. 27, 190- 200. 10.1111/pcmr.12192 24734316 PMC3988474 · DOI
  19. Irion U., Frohnhöfer H. G., Krauss J., Çolak Champollion T., Maischein H.-M., Geiger-Rudolph S., Weiler C. and Nüsslein-Volhard C. (2014a). Gap junctions composed of connexins 41.8 and 39.4 are essential for colour pattern formation in zebrafish. eLife 3, e05125 10.7554/eLife.05125 25535837 PMC4296512 · DOI · Paper page
  20. Irion U., Krauss J. and Nüsslein-Volhard C. (2014b). Precise and efficient genome editing in zebrafish using the CRISPR/Cas9 system. Development 141, 4827- 4830. 10.1242/dev.115584 25411213 PMC4299274 · DOI
  21. Irion U., Singh A. P. and Nüsslein-Volhard C. (2016). The Developmental Genetics of Vertebrate Color Pattern Formation: Lessons from Zebrafish. Curr. Top. Dev. Biol. 117, 141- 169. 10.1016/bs.ctdb.2015.12.012 26969976 · DOI · Paper page
  22. Iwashita M., Watanabe M., Ishii M., Chen T., Johnson S. L., Kurachi Y., Okada N. and Kondo S. (2006). Pigment pattern in jaguar/obelix zebrafish is caused by a Kir7.1 mutation: implications for the regulation of melanosome movement. PLoS Genet. 2, e197 10.1371/journal.pgen.0020197 17121467 PMC1657052 · DOI · Paper page
  23. Kane D. A. and Kishimoto T. (2002). Cell labeling and transplantation techniques. In Zebrafish: A Practical Approach (ed. Nüsslein-Volhard C. and Dahm R.), pp. 95- 119. New York: Oxford University Press.
  24. Kelsh R. N. (2004). Genetics and evolution of pigment patterns in fish. Pigment Cell Res. 17, 326- 336. 10.1111/j.1600-0749.2004.00174.x 15250934 · DOI
  25. Krauss J., Frohnhöfer H. G., Walderich B., Maischein H.-M., Weiler C., Irion U. and Nüsslein-Volhard C. (2014). Endothelin signalling in iridophore development and stripe pattern formation of zebrafish. Biol. Open 3, 503- 509. 10.1242/bio.20148441 24857848 PMC4058085 · DOI · Paper page
  26. Lister J. A., Robertson C. P., Lepage T., Johnson S. L. and Raible D. W. (1999). nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate. Development 126, 3757- 3767. 10433906
  27. 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. et al. (2008). Leukocyte tyrosine kinase functions in pigment cell development. PLoS Genet. 4, e1000026 10.1371/journal.pgen.1000026 18369445 PMC2265441 · DOI · Paper page
  28. Maderspacher F. and Nüsslein-Volhard C. (2003). Formation of the adult pigment pattern in zebrafish requires leopard and obelix dependent cell interactions. Development 130, 3447- 3457. 10.1242/dev.00519 12810592 · DOI · Paper page
  29. Mahalwar P., Walderich B., Singh A. P. and Nüsslein-Volhard C. (2014). Local reorganization of xanthophores fine-tunes and colors the striped pattern of zebrafish. Science 345, 1362- 1364. 10.1126/science.1254837 25214630 · DOI
  30. Mongera A., Singh A. P., Levesque M. P., Chen Y.-Y., Konstantinidis P. and Nüsslein-Volhard C. (2013). Genetic lineage labeling in zebrafish uncovers novel neural crest contributions to the head, including gill pillar cells. Development 140, 916- 925. 10.1242/dev.091066 23362350 · DOI
  31. Mosimann C., Kaufman C. K., Li P., Pugach E. K., Tamplin O. J. and Zon L. I. (2011). Ubiquitous transgene expression and Cre-based recombination driven by the ubiquitin promoter in zebrafish. Development 138, 169- 177. 10.1242/dev.059345 21138979 PMC2998170 · DOI
  32. Nakamasu A., Takahashi G., Kanbe A. and Kondo S. (2009). Interactions between zebrafish pigment cells responsible for the generation of Turing patterns. Proc. Natl. Acad. Sci. USA 106, 8429- 8434. 10.1073/pnas.0808622106 19433782 PMC2689028 · DOI · Paper page
  33. Parichy D. M. (2006). Evolution of danio pigment pattern development. Heredity (Edinb) 97, 200- 210. 10.1038/sj.hdy.6800867 16835593 · DOI
  34. Parichy D. M. and Spiewak J. E. (2015). Origins of adult pigmentation: diversity in pigment stem cell lineages and implications for pattern evolution. Pigment Cell Melanoma Res. 28, 31- 50. 10.1111/pcmr.12332 25421288 PMC4276524 · DOI
  35. Parichy D. M., Mellgren E. M., Rawls J. F., Lopes S. S., Kelsh R. N. and Johnson S. L. (2000a). Mutational analysis of endothelin receptor b1 (rose) during neural crest and pigment pattern development in the zebrafish Danio rerio. Dev. Biol. 227, 294- 306. 10.1006/dbio.2000.9899 11071756 · DOI · Paper page
  36. Parichy D. M., Ransom D. G., Paw B., Zon L. I. and Johnson S. L. (2000b). 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
  37. Parichy D. M., Elizondo M. R., Mills M. G., Gordon T. N. and Engeszer R. E. (2009). Normal table of postembryonic zebrafish development: staging by externally visible anatomy of the living fish. Dev. Dyn. 238, 2975- 3015. 10.1002/dvdy.22113 19891001 PMC3030279 · DOI · Paper page
  38. Patterson L. B. and Parichy D. M. (2013). Interactions with iridophores and the tissue environment required for patterning melanophores and xanthophores during zebrafish adult pigment stripe formation. PLoS Genet. 9, e1003561 10.1371/journal.pgen.1003561 23737760 PMC3667786 · DOI · Paper page
  39. Rodrigues F. S. L. M., Doughton G., Yang B. and Kelsh R. N. (2012). A novel transgenic line using the Cre-lox system to allow permanent lineage-labeling of the zebrafish neural crest. Genesis 50, 750- 757. 10.1002/dvg.22033 22522888 · DOI
  40. Schindelin J., Arganda-Carreras I., Frise E., Kaynig V., Longair M., Pietzsch T., Preibisch S., Rueden C., Saalfeld S., Schmid B. et al. (2012). Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676- 682. 10.1038/nmeth.2019 22743772 PMC3855844 · DOI · Paper page
  41. Singh A. P. and Nüsslein-Volhard C. (2015). Zebrafish stripes as a model for vertebrate colour pattern formation. Curr. Biol. 25, R81- R92. 10.1016/j.cub.2014.11.013 25602311 · DOI · Paper page
  42. Singh A. P., Schach U. and Nüsslein-Volhard C. (2014). Proliferation, dispersal and patterned aggregation of iridophores in the skin prefigure striped colouration of zebrafish. Nat. Cell Biol. 16, 607- 614. 10.1038/ncb2955 24776884 · DOI · Paper page
  43. Singh A. P., Fröhnhofer H. G., Irion U. and Nüsslein-Volhard C. (2015). Fish pigmentation. Response to Comment on “Local reorganization of xanthophores fine-tunes and colors the striped pattern of zebrafish”. Science 348, 297 10.1126/science.aaa2804 25883351 · DOI
  44. Singh A. P., Dinwiddie A., Mahalwar P., Schach U., Linker C., Irion U. and Nüsslein-Volhard C. (2016). Pigment cell progenitors in Zebrafish remain multipotent through metamorphosis. Dev. Cell 38, 316- 330. 10.1016/j.devcel.2016.06.020 27453500 · DOI · Paper page
  45. Walderich B., Singh A. P., Mahalwar P. and Nüsslein-Volhard C. (2016). Homotypic cell competition regulates proliferation and tiling of zebrafish pigment cells during colour pattern formation. Nat. Commun. 7, 11462 10.1038/ncomms11462 27118125 PMC4853480 · DOI
  46. Watanabe M. and Kondo S. (2015). Is pigment patterning in fish skin determined by the Turing mechanism? Trends Genet. 31, 88- 96. 10.1016/j.tig.2014.11.005 25544713 · DOI
  47. Watanabe M., Iwashita M., Ishii M., Kurachi Y., Kawakami A., Kondo S. and Okada N. (2006). Spot pattern of leopard Danio is caused by mutation in the zebrafish connexin41.8 gene. EMBO Rep. 7, 893- 897. 10.1038/sj.embor.7400757 16845369 PMC1559663 · DOI · Paper page
  48. Watanabe M., Sawada R., Aramaki T., Skerrett I. M. and Kondo S. (2015). The physiological characterization of Connexin41.8 and Connexin39.4, which are involved in the stripe pattern formation of zebrafish. J. Biol. Chem. 291, 1053- 1063. 10.1074/jbc.M115.673129 26598520 PMC4714190 · DOI · Paper page
  49. Yamaguchi M., Yoshimoto E. and 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. 10.1073/pnas.0607790104 17360399 PMC1820822 · DOI

Cited by

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Authors
Mahalwar, P., Singh, A. P., Fadeev, A., Nüsslein-Volhard, C., & Irion, U.
Affiliations
  • Max Planck Institute for Developmental Biology (DE)
  • Max Planck Institute for Developmental Biology, Spemannstrasse 35, Tübingen 72076, Germany
Corresponding author
  • Mahalwar, Prateek
  • Irion, Uwe
Venue
Biology Open
Published
2016-11-15
Volume
5
Issue
11
Pages
1680-1690
ISSN
2046-6390 (ISSN-L)
OpenAlex
W2531189335
Cited by
45
References
1
Citations by year
2025: 2 · 2024: 3 · 2023: 7 · 2021: 8 · 2020: 9 · 2019: 6 · 2018: 7 · 2017: 3
FWCI
3.67
Type
journal article
Language
en
Open access
Locations
  • Biology Open (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
Funders
Max-Planck Society
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • 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
Keywords
xanthophores, iridophores, melanophores, cell density, gap junctions

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