title: The basic helix-loop-helix leucine zipper transcription factor Mitf is conserved in Drosophila and functions in eye development.
abstract: The MITF protein is a member of the MYC family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors and is most closely related to the TFE3, TFEC, and TFEB proteins. In the mouse, MITF is required for the development of several different cell types, including the retinal pigment epithelial (RPE) cells of the eye. In Mitf mutant mice, the presumptive RPE cells hyperproliferate, abnormally express the retinal transcriptional regulator Pax6, and form an ectopic neural retina. Here we report the structure of the Mitf gene in Drosophila and demonstrate expression during embryonic development and in the eye-antennal imaginal disc. In vitro, transcriptional regulation by Drosophila Mitf, like its mouse counterpart, is modified by the Eyeless (Drosophila Pax6) transcription factor. In vivo, targeted expression of wild-type or dominant-negative Drosophila Mitf results in developmental abnormalities reminiscent of Mitf function in mouse eye development. Our results suggest that the Mitf gene is the original member of the Mitf-Tfe subfamily of bHLH-Zip proteins and that its developmental function is at least partially conserved between vertebrates and invertebrates. These findings further support the common origin of the vertebrate and invertebrate eyes.
authors.affiliation: Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland.
authors.forename: Jón H
authors.initials: JH
authors.lastname: Hallsson
authors.forename: Benedikta S
authors.initials: BS
authors.lastname: Haflidadóttir
authors.forename: Chad
authors.initials: C
authors.lastname: Stivers
authors.forename: Ward
authors.initials: W
authors.lastname: Odenwald
authors.forename: Heinz
authors.initials: H
authors.lastname: Arnheiter
authors.forename: Francesca
authors.initials: F
authors.lastname: Pignoni
authors.forename: Eiríkur
authors.initials: E
authors.lastname: Steingrímsson
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics*; D019143:Evolution, Molecular; D005123:Eye / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D016678:Genome; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010857:Pigment Epithelium of Eye / Q000196:embryology; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D014157:Transcription Factors