colgate/hdac1 repression of foxd3 expression is required to permit mitfa-dependent melanogenesis

Myron S. Ignatius, Holly E. Moose, Heithem M. El-Hodiri, Paul D. Henion

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Neural crest-derived pigment cell development has been used extensively to study cell fate specification, migration, proliferation, survival and differentiation. Many of the genes and regulatory mechanisms required for pigment cell development are conserved across vertebrates. The zebrafish mutant colgate (col)/histone deacetylase1 (hdac1) has reduced numbers, delayed differentiation and decreased migration of neural crest-derived melanophores and their precursors. In hdac1col mutants normal numbers of premigratory neural crest cells are induced. Later, while there is only a slight reduction in the number of neural crest cells in hdac1col mutants, there is a severe reduction in the number of mitfa-positive melanoblasts suggesting that hdac1 is required for melanoblast specification. Concomitantly, there is a significant increase in and prolonged expression of foxd3 in neural crest cells in hdac1col mutants. We found that partially reducing Foxd3 expression in hdac1col mutants rescues mitfa expression and the melanophore defects in hdac1col mutants. Furthermore, we demonstrate the ability of Foxd3 to physically interact at the mitfa promoter. Because mitfa is required for melanoblast specification and development, our results suggest that hdac1 is normally required to suppress neural crest foxd3 expression thus de-repressing mitfa resulting in melanogenesis by a subset of neural crest-derived cells.

Original languageEnglish (US)
Pages (from-to)568-583
Number of pages16
JournalDevelopmental Biology
Issue number2
StatePublished - Jan 15 2008
Externally publishedYes


  • Histone deacetylase1
  • Melanophore
  • Neural crest
  • Zebrafish
  • c-kit
  • foxd3
  • mitfa

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Developmental Biology


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