THE HOMOTHORAX HOMEOPROTEIN ACTIVATES THE NUCLEAR-LOCALIZATION OF ANOTHER HOMEOPROTEIN, EXTRADENTICLE, AND SUPPRESSES EYE DEVELOPMENT IN DROSOPHILA

The Extradenticle (Exd) protein in Drosophila acts as a cofactor to ho meotic proteins. Its nuclear localization is regulated. We report the cloning of the Drosophila homothorax (hth) gene, a homolog of the mous e Meis1 proto-oncogene that has a homeobox related to that of exd. Com parison with Meis1 finds two regions of high homology: a novel MH doma in and the homeodomain. In imaginal discs, hth expression coincides wi th nuclear Exd. hth and exd also have virtually identical, mutant clon al phenotypes in adults. These results suggest that hth and exd functi on in the same pathway. We show that hth acts upstream of exd and is r equired and sufficient for Exd protein nuclear localization. We also s how that hth and exd are both negative regulators of eye development; their mutant clones caused ectopic eye formation. Targeted expression of hth, but not of exd, in the eye disc abolished eye development comp letely. We suggest that hth acts with exd to delimit the eye field and prevent inappropriate eye development.