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

Development. 2023 Oct 1;150(19):dev202114. doi: 10.1242/dev.202114. Epub 2023 Oct 12.

Abstract

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.

Keywords: CRISPR/Cas9; Chromatophore; Melanocyte; Paired-type homeobox; Pigmentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Regulatory Networks
  • Mammals / genetics
  • Melanocytes / metabolism
  • Mutation
  • Neural Crest / metabolism
  • Oryzias* / genetics
  • Oryzias* / metabolism
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zebrafish* / genetics
  • Zebrafish* / metabolism

Substances

  • SOXE Transcription Factors
  • Zebrafish Proteins
  • sox10 protein, zebrafish
  • pax3a protein, zebrafish