NUCLEAR TRANSLOCATION OF EXTRADENTICLE REQUIRES HOMOTHORAX, WHICH ENCODES AN EXTRADENTICLE-RELATED HOMEODOMAIN PROTEIN

We show that homothorax (hth) is required for the Hox genes to pattern the body of the fruit fly, Drosophila melanogaster, hth is necessary for the nuclear localization of an essential HOX cofactor, Extradentic le (EXD), and encodes a homeodomain protein that shares extensive iden tity with the product of Meis1, a murine proto-oncogene. MEIS1 is able to rescue hth mutant phenotypes and can induce the cytoplasmic-to-nuc lear translocation of EXD in cell culture and Drosophila embryos. Thus , Meis1 is a murine homolog of hth. MEIS1/HTH also specifically binds to EXD with high affinity in vitro. These data suggest a novel and evo lutionarily conserved mechanism for regulating HOX activity in which a direct protein-protein interaction between EXD and HTH results in EXD 's nuclear translocation.