Transcription factor Ap-2alpha is necessary for development of embryonic melanophores, autonomic neurons and pharyngeal skeleton in zebrafish.
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.
O'Brien
Erin K
EK
Department of Otolaryngology, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
d'Alençon
Claudia
C
Bonde
Gregory
G
Li
Wei
W
Schoenebeck
Jeff
J
Allende
Miguel L
ML
Gelb
Bruce D
BD
Yelon
Deborah
D
Eisen
Judith S
JS
Cornell
Robert A
RA
D000595:Amino Acid Sequence; D000818:Animals; D016375:Antisense Elements (Genetics); D017776:Autonomic Pathways / Q000196:embryology*; D001934:Branchial Region / Q000196:embryology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008547:Melanophores / Q000502:physiology*; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000196:embryology; D019009:Proto-Oncogene Proteins c-kit; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins
D016375:Antisense Elements (Genetics); D004268:DNA-Binding Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D029961:Zebrafish Proteins; C493676:tfap2a protein, zebrafish; D019009:Proto-Oncogene Proteins c-kit