Phenotypic suppression of empty spiracles is prevented by buttonhead

Unlike the trunk segments, the anterior head segments of Drosophila are formed in the absence of pair-rule(1,2) and HOX-cluster gene(3) expression, by the activities of the gap-like genes orthodenticle (otd), empty spiracles (ems) and buttonhead (btd)(4,5). The products of these genes are transcription factors(6,7), but only EMS has a HOX-like homeodomain(8,9). Indeed, ems can confer identity to trunk segments(10) when other HOX-cluster gene activities are absent(3,11). In trunk segments of wild-type embryos, however, ems activity is prevented by phenotypic suppression(10), in which more posterior HOX-cluster genes inactivate the more anterior without affecting transcription or translation(12). ems is suppressed by all other Hox-cluster genes and so is placed at the bottom of their hierarchy(10). Here we show that misexpression of EMS in the head transforms segment identity in a btd-dependent manner, that misexpression of BTD in the trunk causes ems-dependent structures to develop, and that EMS and BTD interact in vitro. The data indicate that this interaction may allow ems to escape from the bottom of the HOX-cluster gene hierarchy and cause a dominant switch of homeotic prevalence in the anterior-posterior direction.