A gene regulatory network combining Pax3/7, Sox10 and Mitf generates diverse pigment cell types in medaka and zebrafish

Motohiro Miyadai, Hiroyuki Takada, Akiko Shiraishi, Tetsuaki Kimura, Ikuko Watakabe, Hikaru Kobayashi, Yusuke Nagao, Kiyoshi Naruse, Shin Ichi Higashijima, Takashi Shimizu, Robert N. Kelsh, Masahiko Hibi, Hisashi Hashimoto

Research output: Contribution to journalArticlepeer-review

2 Citations (SciVal)


Neural crest cells generate numerous derivatives, including pigment cells, and are a model for studying how fate specification from multipotent progenitors is controlled. In mammals, the core gene regulatory network for melanocytes (their only pigment cell type) contains three transcription factors, Sox10, Pax3 and Mitf, with the latter considered a master regulator of melanocyte development. In teleosts, which have three to four pigment cell types (melanophores, iridophores and xanthophores, plus leucophores e.g. in medaka), gene regulatory networks governing fate specification are poorly understood, although Mitf function is considered conserved. Here, we show that the regulatory relationships between Sox10, Pax3 and Mitf are conserved in zebrafish, but the role for Mitf is more complex than previously emphasized, affecting xanthophore development too. Similarly, medaka Mitf is necessary for melanophore, xanthophore and leucophore formation. Furthermore, expression patterns and mutant phenotypes of pax3 and pax7 suggest that Pax3 and Pax7 act sequentially, activating mitf expression. Pax7 modulates Mitf function, driving co-expressing cells to differentiate as xanthophores and leucophores rather than melanophores. We propose that pigment cell fate specification should be considered to result from the combinatorial activity of Mitf with other transcription factors.

Original languageEnglish
Article numberdev202114
JournalDevelopment (Cambridge)
Issue number19
Early online date12 Oct 2023
Publication statusPublished - 31 Oct 2023

Bibliographical note

Funding Information:
This study was supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (20K06757 to H.H.). Open access funding provided by Nagoya University. Deposited in PMC for immediate release.


  • Chromatophore
  • CRISPR/Cas9
  • Melanocyte
  • Paired-type homeobox
  • Pigmentation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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