ZFIN ID: ZDB-PUB-010813-3
Duplicate mitf genes in zebrafish: complementary expression and conservation of melanogenic potential
Lister, J., Close, J., and Raible, D.
Date: 2001
Source: Developmental Biology   237(2): 333-344 (Journal)
Registered Authors: Lister, James A., Raible, David
Keywords: Mitf; microphthalmia; retinal pigment epithelium; neural crest; melanocyte; gene duplication; evolution; nacre; TFE3
MeSH Terms:
  • 3T3 Cells
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cells, Cultured
  • Cloning, Molecular
  • DNA-Binding Proteins/biosynthesis
  • DNA-Binding Proteins/chemistry*
  • DNA-Binding Proteins/genetics*
  • DNA-Binding Proteins/physiology
  • Exons
  • In Situ Hybridization
  • Luciferases/metabolism
  • Melanocytes/metabolism*
  • Mice
  • Microphthalmia-Associated Transcription Factor
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation*
  • Phylogeny
  • Protein Isoforms
  • RNA, Messenger/metabolism
  • Radiation Hybrid Mapping
  • Sequence Homology, Amino Acid
  • Time Factors
  • Transcription Factors/biosynthesis
  • Transcriptional Activation
  • Transfection
  • Zebrafish
  • Zebrafish Proteins
PubMed: 11543618 Full text @ Dev. Biol.
Mutations in the zebrafish nacre/mitfa gene, expressed in all embryonic melanogenic cells, perturb only neural crest melanocytes, suggesting redundancy of mitfa with another gene in the zebrafish retinal pigment epithelium (RPE). Here, we describe a second zebrafish mitf gene, mitfb, which may fulfill this role. The proteins encoded by the two zebrafish mitf genes appear homologous to distinct isoforms generated by alternately spliced mRNAs of the single mammalian Mitf gene, suggesting specialization of the two zebrafish genes following a duplication event. Consistent with this hypothesis, expression of mitfa and mitfb is partially overlapping. mitfb is coexpressed with mitfa in the RPE at an appropriate time to compensate for loss of mitfa function in the nacre mutant but is not expressed in neural crest melanoblasts. Additionally, mitfb is expressed in the epiphysis and olfactory bulb where mitfa is not, and where Mitf expression has not previously been reported in other species. mitfb, but not a zebrafish ortholog of the closely related gene tfe3, can rescue neural crest melanophore development in nacre/mitfa mutant embryos when expressed via the mitfa promoter. These data suggest that mitfa and mitfb together may recapitulate the expression and functions of a single ancestral Mitf gene, and that mitfb may serve additional novel functions