Pai C Y, Kuo T S, Jaw T J, Kurant E, Chen C T, Bessarab D A, Salzberg A, Sun Y H
Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan, Republic of China.
Genes Dev. 1998 Feb 1;12(3):435-46. doi: 10.1101/gad.12.3.435.
The Extradenticle (Exd) protein in Drosophila acts as a cofactor to homeotic proteins. Its nuclear localization is regulated. We report the cloning of the Drosophila homothorax (hth) gene, a homolog of the mouse Meis1 proto-oncogene that has a homeobox related to that of exd. Comparison with Meis1 finds two regions of high homology: a novel MH domain and the homeodomain. In imaginal discs, hth expression coincides with nuclear Exd. hth and exd also have virtually identical, mutant clonal phenotypes in adults. These results suggest that hth and exd function in the same pathway. We show that hth acts upstream of exd and is required and sufficient for Exd protein nuclear localization. We also show 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 completely. We suggest that hth acts with exd to delimit the eye field and prevent inappropriate eye development.
果蝇中的额外齿状蛋白(Exd)作为同源异型蛋白的辅因子发挥作用。其核定位受到调控。我们报告了果蝇同胸节(hth)基因的克隆,该基因是小鼠Meis1原癌基因的同源物,具有与exd相关的同源异型框。与Meis1比较发现两个高度同源的区域:一个新的MH结构域和同源异型结构域。在成虫盘里,hth的表达与核内的Exd一致。hth和exd在成虫中也具有几乎相同的突变克隆表型。这些结果表明hth和exd在同一途径中发挥作用。我们发现hth在exd的上游起作用,是Exd蛋白核定位所必需且足够的。我们还表明hth和exd都是眼睛发育的负调节因子;它们的突变克隆导致异位眼的形成。在眼盘中靶向表达hth而非exd会完全消除眼睛发育。我们认为hth与exd共同作用来界定眼区并防止不适当的眼睛发育。