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Cited by 118melanin and skin pigmentationDevelopmental Biology and Gene RegulationZebrafish Biomedical Research Applications

Foxd3 controls melanophore specification in the zebrafish neural crest by regulation of Mitf

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Curran, Kevin, Raible, David W., Lister, James A.·2009·Developmental Biology
DOI 10.1016/j.ydbio.2009.06.010PMC PMC2716409
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Abstract

We describe a mechanistic model whereby Foxd3, a forkhead transcription factor, prevents neural crest-derived precursors from acquiring a melanophore fate. Foxd3 regulates this fate choice by repressing the mitfa promoter in a subset of neural crest cells. mitfa is only expressed in a Foxd3-negative subset of neural crest cells, and foxd3 mutants show an increase in the spatial domain of mitfa expression, thereby suggesting that Foxd3 limits the mitfa domain. Furthermore, foxd3:gfp transgenic zebrafish reveal foxd3 expression in xanthophore precursors and iridophores, but not in terminally differentiated melanophores. Luciferase experiments and embryo mRNA injections indicate Foxd3 acts directly on the mitfa promoter to negatively regulate mitfa expression. Taken together, our data suggests the presence of Foxd3 in a subset of precursors leads to mitfa repression and suppression of melanophore fate. MITF, the human mitfa ortholog, has recently been described as an oncogene and implicated in various forms of melanoma. Understanding the mechanisms that regulate mitfa and melanophore development could prove informative in the treatment and prevention of these human diseases.

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  • mitfa is expressed initially in almost all neural crest cells.

    “with mitfa being expressed initially in almost all NC cells [32]”

    From A systems biology approach uncovers the core gene regulatory network governing iridophore fate choice from the neural crest (2018) · cites this paper as [32]

    The Introduction (page unavailable) says that, in wild-type zebrafish, mitfa is expressed only in a subset of neural crest cells, not almost all of them. The Results section on migratory neural crest cells (page unavailable) also reports that mitfa and Foxd3 are largely mutually exclusive even at the earliest stages of reporter expression. (LLM, conf=0.87)

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    Experimental — accuracy not yet measured

  • In the WT context, Sox10 and Tfec stay upregulated in mature pigment cells, Ltk and Pnp4a increase and reach positive steady-state, and Mitfa initially rises rapidly then drops to a lower level at differentiation stages.

    “Specifically, in the WT context, it was crucial that Sox10 and Tfec stay upregulated in mature pigment cells, i.e. reach a positive steady-state. Similarly, Ltk and Pnp4a concentrations should increase and reach a positive steady-state. Mitfa levels should initially rise rapidly, reflecting the widespread expression of mitfa in all pigment cell progenitors [32], but should then drop to a distinct”

    From A systems biology approach uncovers the core gene regulatory network governing iridophore fate choice from the neural crest (2018) · cites this paper as [32]

    The Introduction says Mitf is among the earliest genes expressed in melanoblast precursors, and the Results section on the mitfa:gfp line documents early mitfa expression in cells identified as melanoblasts (no page numbers supplied). These passages support early expression, but not the cited phrase’s claim that mitfa is expressed in all pigment-cell progenitors. The citation is attached to that phrase, not to the surrounding steady-state predictions. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Several requirements for iridophore development from the neural crest are known.

    “Several requirements for iridophore development from the neural crest are known [5], [26], [27].”

    From Gene Expression Analysis of Zebrafish Melanocytes, Iridophores, and Retinal Pigmented Epithelium Reveals Indicators of Biological Function and Developmental Origin (2013) · cites this paper as [26]

  • Previous analyses using a foxd3:gfp transgenic line suggested that Foxd3 is expressed in mature iridophores.

    “Previous analyses using a foxd3:gfp transgenic line have suggested that Foxd3 is expressed in mature iridophores [32].”

    From A systems biology approach uncovers the core gene regulatory network governing iridophore fate choice from the neural crest (2018) · cites this paper as [32]

  • ltk, ednrb1, and pnp4a are known to be important for iridophore development.

    “Included in this enrichment list are several factors known to be important for iridophore development, including ltk, ednrb1, and pnp4a [5], [26], [27].”

    From Gene Expression Analysis of Zebrafish Melanocytes, Iridophores, and Retinal Pigmented Epithelium Reveals Indicators of Biological Function and Developmental Origin (2013) · cites this paper as [26]

    The Discussion says Foxd3 appears to promote iridophore specification, but it does not address whether ltk, ednrb1, or pnp4a are important for iridophore development. Searches of our copy for those gene names and their expanded terms found no passage establishing the attributed claim. The indexed passages provide no page numbers. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 55

  1. Alkhateeb A Fain PR Spritz RA 2005 Candidate functional promoter variant in the FOXD3 melanoblast developmental regulator gene in autosomal dominant vitiligo J Invest Dermatol 125 388 91 16098053
  2. Bondurand N Pingault V Goerich DE Lemort N Sock E Le Caignec C Wegner M Goossens M 2000 Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome Hum Mol Genet 9 1907 17 10942418
  3. Braasch I Salzburger W Meyer A 2006 Asymmetric evolution in two fish-specifically duplicated receptor tyrosine kinase paralogons involved in teleost coloration Mol Biol Evol 23 1192 202 16547150
  4. Clevidence DE Overdier DG Tao W Qian X Pani L Lai E Costa RH 1993 Identification of nine tissue-specific transcription factors of the hepatocyte nuclear factor 3/forkhead DNA-binding-domain family Proc Natl Acad Sci U S A 90 3948 52 7683413 PMC46423
  5. Cooper CD Linbo TH Raible DW 2009 Kit and foxd3 genetically interact to regulate melanophore survival in zebrafish Dev Dyn 238 875 886 19301400 PMC2730777
  6. Cooper CD Raible DW 2009 Mechanisms for reaching the differentiated state: Insights from neural crest-derived melanocytes Semin Cell Dev Biol 20 105 10 18935965 PMC2730768
  7. Dorsky RI Raible DW Moon RT 2000 Direct regulation of nacre, a zebrafish MITF homolog required for pigment cell formation, by the Wnt pathway Genes Dev 14 158 62 10652270 PMC316348
  8. Dutton KA Pauliny A Lopes SS Elworthy S Carney TJ Rauch J Geisler R Haffter P Kelsh RN 2001 Zebrafish colourless encodes sox10 and specifies non-ectomesenchymal neural crest fates Development 128 4113 25 11684650
  9. Elworthy S Lister JA Carney TJ Raible DW Kelsh RN 2003 Transcriptional regulation of mitfa accounts for the sox10 requirement in zebrafish melanophore development Development 130 2809 18 12736222
  10. Fujii R 2000 The regulation of motile activity in fish chromatophores Pigment Cell Res 13 300 19 11041206
  11. Gilmour DT Maischein HM Nusslein-Volhard C 2002 Migration and function of a glial subtype in the vertebrate peripheral nervous system Neuron 34 577 88 12062041
  12. Hacker U Kaufmann E Hartmann C Jurgens G Knochel W Jackle H 1995 The Drosophila fork head domain protein crocodile is required for the establishment of head structures Embo J 14 5306 17 7489720 PMC394640
  13. Hanna LA Foreman RK Tarasenko IA Kessler DS Labosky PA 2002 Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo Genes Dev 16 2650 61 12381664 PMC187464
  14. Harris ML Erickson CA 2007 Lineage specification in neural crest cell pathfinding Dev Dyn 236 1 19 16894594
  15. Hoekstra HE 2006 Genetics, development and evolution of adaptive pigmentation in vertebrates Heredity 97 222 34 16823403
  16. Holland PW Garcia-Fernandez J Williams NA Sidow A 1994 Gene duplications and the origins of vertebrate development Dev Suppl 125 33 7579513
  17. Hromas R Ye H Spinella M Dmitrovsky E Xu D Costa RH 1999 Genesis, a Winged Helix transcriptional repressor, has embryonic expression limited to the neural crest, and stimulates proliferation in vitro in a neural development model Cell Tissue Res 297 371 82 10460485
  18. Ignatius MS Moose HE El-Hodiri HM Henion PD 2008 colgate/hdac1 Repression of foxd3 expression is required to permit mitfa-dependent melanogenesis Dev Biol 313 568 83 18068699 PMC2700343
  19. Julich D Hwee Lim C Round J Nicolaije C Schroeder J Davies A Geisler R Lewis J Jiang YJ Holley SA 2005 beamter/deltaC and the role of Notch ligands in the zebrafish somite segmentation, hindbrain neurogenesis and hypochord differentiation Dev Biol 286 391 404 16125692
  20. Kelsh RN 2004 Genetics and evolution of pigment patterns in fish Pigment Cell Res 17 326 36 15250934
  21. Kelsh RN Dutton K Medlin J Eisen JS 2000 Expression of zebrafish fkd6 in neural crest-derived glia Mech Dev 93 161 4 10781949
  22. Kimmel CB Ballard WW Kimmel SR Ullmann B Schilling TF 1995 Stages of embryonic development of the zebrafish Dev Dyn 203 253 310 8589427
  23. Kos R Reedy MV Johnson RL Erickson CA 2001 The winged-helix transcription factor FoxD3 is important for establishing the neural crest lineage and repressing melanogenesis in avian embryos Development 128 1467 79 11262245
  24. LaBonne C Bronner-Fraser M 2000 Snail-related transcriptional repressors are required in Xenopus for both the induction of the neural crest and its subsequent migration Dev Biol 221 195 205 10772801
  25. Labosky PA Kaestner KH 1998 The winged helix transcription factor Hfh2 is expressed in neural crest and spinal cord during mouse development Mech Dev 76 185 90 9767163
  26. Larue L Delmas V 2006 The WNT/Beta-catenin pathway in melanoma Front Biosci 11 733 42 16146765
  27. Lee HC Huang HY Lin CY Chen YH Tsai HJ 2006 Foxd3 mediates zebrafish myf5 expression during early somitogenesis Dev Biol 290 359 72 16386728
  28. Lee M Goodall J Verastegui C Ballotti R Goding CR 2000 Direct regulation of the Microphthalmia promoter by Sox10 links Waardenburg-Shah syndrome (WS4)-associated hypopigmentation and deafness to WS2 J Biol Chem 275 37978 83 10973953
  29. Lei TC Virador V Yasumoto K Vieira WD Toyofuku K Hearing VJ 2002 Stimulation of melanoblast pigmentation by 8-methoxypsoralen:the involvement of microphthalmia-associated transcription factor, the protein kinase a signal pathway, and proteasome-mediated degradation J Invest Dermatol 119 1341 9 12485437
  30. Levy C Khaled M Fisher DE 2006 MITF: master regulator of melanocyte development and melanoma oncogene Trends Mol Med 12 406 14 16899407
  31. Lister JA Close J Raible DW 2001 Duplicate mitf genes in zebrafish: complementary expression and conservation of melanogenic potential Dev Biol 237 333 44 11543618
  32. Lister JA Cooper C Nguyen K Modrell M Grant K Raible DW 2006 Zebrafish Foxd3 is required for development of a subset of neural crest derivatives Dev Biol 290 92 104 16364284
  33. Lister JA Robertson CP Lepage T Johnson SL Raible DW 1999 nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate Development 126 3757 67 10433906
  34. McGill GG Horstmann M Widlund HR Du J Motyckova G Nishimura EK Lin YL Ramaswamy S Avery W Ding HF Jordan SA Jackson IJ Korsmeyer SJ Golub TR Fisher DE 2002 Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability Cell 109 707 18 12086670
  35. Minchin JE Hughes SM 2008 Sequential actions of Pax3 and Pax7 drive xanthophore development in zebrafish neural crest Dev Biol 317 508 22 18417109 PMC3005709
  36. Montero-Balaguer M Lang MR Sachdev SW Knappmeyer C Stewart RA De La Guardia A Hatzopoulos AK Knapik EW 2006 The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish Dev Dyn 235 3199 212 17013879
  37. Odenthal J Nusslein-Volhard C 1998 fork head domain genes in zebrafish Dev Genes Evol 208 245 58 9683740
  38. Parichy DM 2006 Evolution of danio pigment pattern development Heredity 97 200 10 16835593
  39. Park HC Boyce J Shin J Appel B 2005 Oligodendrocyte specification in zebrafish requires notch-regulated cyclin-dependent kinase inhibitor function J Neurosci 25 6836 44 16033893 PMC6725353
  40. Planque N Raposo G Leconte L Anezo O Martin P Saule S 2004 Microphthalmia transcription factor induces both retinal pigmented epithelium and neural crest melanocytes from neuroretina cells J Biol Chem 279 41911 7 15277526
  41. Pohl BS Knochel W 2001 Overexpression of the transcriptional repressor FoxD3 prevents neural crest formation in Xenopus embryos Mech Dev 103 93 106 11335115
  42. Potterf SB Furumura M Dunn KJ Arnheiter H Pavan WJ 2000 Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3 Hum Genet 107 1 6 10982026
  43. Saito H Yasumoto K Takeda K Takahashi K Yamamoto H Shibahara S 2003 Microphthalmia-associated transcription factor in the Wnt signaling pathway Pigment Cell Res 16 261 5 12753399
  44. Sasai N Mizuseki K Sasai Y 2001 Requirement of FoxD3-class signaling for neural crest determination in Xenopus Development 128 2525 36 11493569
  45. Steiner AB Engleka MJ Lu Q Piwarzyk EC Yaklichkin S Lefebvre JL Walters JW Pineda-Salgado L Labosky PA Kessler DS 2006 FoxD3 regulation of Nodal in the Spemann organizer is essential for Xenopus dorsal mesoderm development Development 133 4827 38 17092955 PMC1676154
  46. Steingrimsson E Copeland NG Jenkins NA 2004 Melanocytes and the microphthalmia transcription factor network Annu Rev Genet 38 365 411 15568981
  47. Stewart RA Arduini BL Berghmans S George RE Kanki JP Henion PD Look AT 2006 Zebrafish foxd3 is selectively required for neural crest specification, migration and survival Dev Biol 292 174 88 16499899
  48. Sutton J Costa R Klug M Field L Xu D Largaespada DA Fletcher CF Jenkins NA Copeland NG Klemsz M Hromas R 1996 Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells J Biol Chem 271 23126 33 8798505
  49. Sviderskaya EV Wakeling WF Bennett DC 1995 A cloned, immortal line of murine melanoblasts inducible to differentiate to melanocytes Development 121 1547 57 7540532
  50. Tachibana M Takeda K Nobukuni Y Urabe K Long JE Meyers KA Aaronson SA Miki T 1996 Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics Nat Genet 14 50 4 8782819
  51. Teng L Mundell NA Frist AY Wang Q Labosky PA 2008 Requirement for Foxd3 in the maintenance of neural crest progenitors Development 135 1615 24 18367558 PMC2562748
  52. Thomas AJ Erickson CA 2009 FOXD3 regulates the lineage switch between neural crest-derived glial cells and pigment cells by repressing MITF through a non-canonical mechanism Development 136 1849 58 19403660 PMC2680109
  53. Verastegui C Bille K Ortonne JP Ballotti R 2000 Regulation of the microphthalmia-associated transcription factor gene by the Waardenburg syndrome type 4 gene, SOX10 J Biol Chem 275 30757 60 10938265
  54. Watanabe A Takeda K Ploplis B Tachibana M 1998 Epistatic relationship between Waardenburg syndrome genes MITF and PAX3 Nat Genet 18 283 6 9500554
  55. Yaklichkin S Steiner AB Lu Q Kessler DS 2007 FoxD3 and Grg4 physically interact to repress transcription and induce mesoderm in Xenopus J Biol Chem 282 2548 57 17138566 PMC1780074

Cited by

Sorted by citations

Authors
Curran, K., Raible, D. W., & Lister, J. A.
Affiliations
  • University of Washington (US)
  • Virginia Commonwealth University (US)
Corresponding author
  • Raible, David W.
  • Lister, James A.
ORCID
Raible, David W.
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2009-08
Volume
332
Issue
2
Pages
408-417
ISSN
0012-1606 (ISSN-L)
DOI
10.1016/j.ydbio.2009.06.010
PMC
PMC2716409
OpenAlex
W2165389148
Cited by
118
References
1
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 3 · 2019: 8 · 2018: 9 · 2017: 14 · 2016: 9 · 2015: 4 · 2014: 4 · 2013: 9 · 2012: 9
FWCI
3.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Washington Research Foundation
  • Achievement Rewards for College Scientists Foundation
  • Fondation ARC pour la Recherche sur le Cancer
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS045246)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007183)
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
FOXD3, MITF, mitfa, neural crest, xanthophores, iridophores, transcriptional repression, melanocyte differentiation, zebrafish, melanoma
MeSH terms
Animals, Cells, Cultured, Humans, Melanophores, Neural Crest, Promoter Regions, Genetic, Recombinant Fusion Proteins, Zebrafish, Gene Expression Regulation, Developmental, Zebrafish Proteins, Animals, Genetically Modified, NIH 3T3 Cells, Mice, Microphthalmia-Associated Transcription Factor, Forkhead Transcription Factors

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