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Interplay between Foxd3 and Mitf regulates cell fate plasticity in the zebrafish neural crest.

Pigment cells of the zebrafish, Danio rerio, offer an exceptionally tractable system for studying the genetic and cellular bases of cell fate decisions. In the zebrafish, neural crest cells generate three types of pigment cells during embryogenesis: yellow xanthophores, iridescent iridophores and black melanophores. In this study, we present evidence for a model whereby melanophores and iridophores descend from a common precursor whose fate is regulated by an interplay between the transcription factors Mitf and Foxd3. Loss of mitfa, a key regulator of melanophore development, resulted in supernumerary ectopic iridophores while loss of foxd3, a mitfa repressor, resulted in fewer iridophores. Double mutants showed a restoration of iridophores, suggesting that one of Foxd3's roles is to suppress mitfa to promote iridophore development. Foxd3 co-localized with pnp4a, a novel marker of early iridophore development, and was necessary for its expression. A considerable overlap was found between iridoblast and melanoblast markers but not xanthoblast markers, which resolved as cells began to differentiate. Cell lineage analyses using the photoconvertible marker, EosFP, revealed that both melanophores and iridophores develop from a mitfa+ precursor. Taken together, our data reveal a Foxd3/mitfa transcriptional switch that governs whether a bi-potent pigment precursor will attain either an iridophore or a melanophore fate.

Pubmed ID: 20460180


  • Curran K
  • Lister JA
  • Kunkel GR
  • Prendergast A
  • Parichy DM
  • Raible DW


Developmental biology

Publication Data

August 1, 2010

Associated Grants

  • Agency: NINDS NIH HHS, Id: R01 NS045246
  • Agency: NINDS NIH HHS, Id: R01 NS045246-01
  • Agency: NINDS NIH HHS, Id: R01 NS045246-02
  • Agency: NINDS NIH HHS, Id: R01 NS045246-03
  • Agency: NINDS NIH HHS, Id: R01 NS045246-04
  • Agency: NINDS NIH HHS, Id: R01 NS057220
  • Agency: NINDS NIH HHS, Id: R01 NS057220-01A1
  • Agency: NINDS NIH HHS, Id: R01 NS057220-02
  • Agency: NINDS NIH HHS, Id: R01 NS057220-03
  • Agency: NINDS NIH HHS, Id: R01 NS057220-04
  • Agency: NICHD NIH HHS, Id: T32 HD007183

Mesh Terms

  • Animals
  • Animals, Genetically Modified
  • Cell Lineage
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Developmental
  • Melanocytes
  • Microphthalmia-Associated Transcription Factor
  • Microscopy, Fluorescence
  • Models, Biological
  • Models, Genetic
  • Mutation
  • Neural Crest
  • Phylogeny
  • Pigmentation
  • Zebrafish
  • Zebrafish Proteins