Mutational analysis of the Drosophila homothorax gene

The homothorax (hth) gene is involved in multiple aspects of embryonic and adult fly development. It encodes a homeodomain-containing protein of the M EIS family and was shown to regulate the subcellular localization of the ho meotic protein cofactor Extradenticle (EXD). The HTH protein contains a TAL E class homeodomain and a conserved MH domain, which is required for its in teraction with EXD. In this work, we describe the structure of the hth locu s, characterize at the molecular level a collection of mutant alleles of ht h, and discuss the correlation between the identified structural defects an d their consequent phenotypes. The hth locus spans more than 100 kb and con tains 14 exons. Several of the exon-intron boundaries within the homeodomai n and the MH domain-coding regions are conserved between Drosophila and Cae norhabditis elegans. The analysis of hth mutations demonstrates that the ho meodomain of HTH is not required for nuclear localization of EXD and that t he MH domain-containing first 240 residues are sufficient for nuclear local ization of both EXD and HTH. Mutations that alter or delete the homeodomain cause only partial homeotic transformations in the PNS, whereas mutations affecting the MH domain cause distinct and more severe PNS phenotypes. Thes e observations may suggest that driving nuclear localization of EXD is the main role of HTH in patterning the embryonic PNS. They may also suggest tha t homeodomain-defective HTH protein retains some of its transcription-regul ating functions by binding DNA via its interaction with EXD.