Transcription factor Ap-2alpha is necessary for development of embryonic melanophores, autonomic neurons and pharyngeal skeleton in zebrafish

Erin K O'Brien, Claudia d'Alençon, Gregory Bonde, Wei Li, Jeffrey Schoenebeck, Miguel L Allende, Bruce D Gelb, Deborah Yelon, Judith S Eisen, Robert A Cornell

Research output: Contribution to journalArticlepeer-review


The genes that control development of embryonic melanocytes are poorly defined. Although transcription factor Ap-2alpha is expressed in neural crest (NC) cells, its role in development of embryonic melanocytes and other neural crest derivatives is unclear because mouse Ap-2alpha mutants die before melanogenesis. We show that zebrafish embryos injected with morpholino antisense oligonucleotides complementary to ap-2alpha (ap-2alpha MO) complete early morphogenesis normally and have neural crest cells. Expression of c-kit, which encodes the receptor for the Steel ligand, is reduced in these embryos, and, similar to zebrafish c-kit mutant embryos, embryonic melanophores are reduced in number and migration. The effects of ap-2alpha MO injected into heterozygous and homozygous c-kit mutants support the notion that Ap-2alpha works through C-kit and additional target genes to mediate melanophore cell number and migration. In contrast to c-kit mutant embryos, in ap-2alpha MO-injected embryos, melanophores are small and under-pigmented, and unexpectedly, analysis of mosaic embryos suggests Ap-2alpha regulates melanophore differentiation through cell non-autonomous targets. In addition to melanophore phenotypes, we document reduction of other neural crest derivatives in ap-2alpha MO-injected embryos, including jaw cartilage, enteric neurons, and sympathetic neurons. These results reveal that Ap-2alpha regulates multiple steps of melanophore development, and is required for development of other neuronal and non-neuronal neural crest derivatives.
Original languageEnglish
Pages (from-to)246-61
Number of pages16
JournalDevelopmental Biology
Issue number1
Publication statusPublished - 1 Jan 2004


  • Amino Acid Sequence
  • Animals
  • Antisense Elements (Genetics)
  • Autonomic Pathways
  • Branchial Region
  • DNA-Binding Proteins
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Melanophores
  • Molecular Sequence Data
  • Neural Crest
  • Proto-Oncogene Proteins c-kit
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Transcription Factor AP-2
  • Transcription Factors
  • Zebrafish
  • Zebrafish Proteins


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