Duplicate mitf genes in zebrafish: complementary expression and conservation of melanogenic potential.
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.
Lister
J A
JA
Department of Biological Structure, Center for Developmental Biology, University of Washington, HSB G514, Seattle, Washington 98195-7420, USA. jalister@u.washington.edu
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Raible
D W
DW
D016475:3T3 Cells; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D005091:Exons; D017403:In Situ Hybridization; D008156:Luciferases / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D021101:Radiation Hybrid Mapping; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis; D015533:Transcriptional Activation; D014162:Transfection; D015027:Zebrafish; D029961:Zebrafish Proteins
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; C069203:TFE3 protein, human; D014157:Transcription Factors; D029961:Zebrafish Proteins; C497237:mitfa protein, zebrafish; D008156:Luciferases