Gene structure of the goldfish agouti-signaling protein: a putative role in the dorsal-ventral pigment pattern of fish

Endocrinology. 2005 Mar;146(3):1597-610. doi: 10.1210/en.2004-1346. Epub 2004 Dec 9.


One of the most successful chromatic adaptations in vertebrates is the dorsal-ventral pigment pattern in which the dorsal skin is darkly colored, whereas the ventrum is light. In fish, the latter pattern is achieved because a melanization inhibition factor inhibits melanoblast differentiation and supports iridophore proliferation in the ventrum. In rodents, the patterned pigmentation results from regional production of the agouti-signaling protein (ASP). This peptide controls the switch between production of eumelanin and pheomelanin by antagonizing alphaMSH effects on melanocortin receptor (MCR) 1 in the melanocytes. In addition, ASP inhibits the differentiation and proliferation of melanoblast. Thus, the mammalian ASP may be homologous to the poikilotherm melanization inhibition factor. By screening of a genomic library, we deduced the amino acid sequence of goldfish ASP. The ASP gene is a four-exon gene spanning 3097 bp that encodes a 125-amino acid precursor. Northern blot analysis identified two different ASP mRNAs in ventral skin of red- and black-pigmented and albino fish, but no expression levels were observed in the dorsal skin of the same fish. The dorsal-ventral expression polarity was also detected in both black dorsally pigmented fish and albino fish. Pharmacological studies demonstrate that goldfish ASP acts as a melanocortin antagonist at Fugu MC1R and goldfish MC4R. In addition, goldfish ASP inhibited Nle4, D-Phe7-MSH-stimulated pigment dispersion in medaka melanophores. Our studies support agouti signaling protein as the melanization inhibition factor, a key factor in the development of the dorsal-ventral pigment pattern in fish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti Signaling Protein
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding, Competitive
  • Biological Assay
  • Blotting, Northern
  • Blotting, Southern
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Cloning, Molecular
  • Culture Media, Conditioned / pharmacology
  • Cyclic AMP / metabolism
  • DNA / chemistry
  • Ethidium / pharmacology
  • Female
  • Gene Library
  • Genetic Vectors
  • Goldfish
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Ligands
  • Male
  • Melanins / metabolism
  • Molecular Sequence Data
  • Protein Isoforms
  • RNA / chemistry
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Takifugu
  • Tissue Distribution
  • Transfection
  • alpha-MSH / metabolism


  • Agouti Signaling Protein
  • Culture Media, Conditioned
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Melanins
  • Protein Isoforms
  • RNA, Messenger
  • pheomelanin
  • eumelanin
  • alpha-MSH
  • RNA
  • DNA
  • Cyclic AMP
  • Ethidium