Genetics, Vol. 167, 233-241, May 2004, Copyright © 2004
The Basic Helix-Loop-Helix Leucine Zipper Transcription Factor Mitf Is Conserved in Drosophila and Functions in Eye Development
Jón H. Hallssona,b,
Benedikta S. Haflidadóttira,c,
Chad Stiversd,
Ward Odenwaldd,
Heinz Arnheiterb,
Francesca Pignonic, and
Eiríkur Steingrímssona
a Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland,
b Laboratory of Developmental Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892,
c Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114
d Neural Cell-Fate Determinants Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892
Corresponding author:
Francesca Pignoni, Harvard Medical School and Massachusetts Eye and Ear Infirmary, #507, 243 Charles St., Boston, MA 02114., francesca_pignoni{at}meei.harvard.edu (E-mail)
Communicating editor: C. A. KOZAK
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.
