Molecular basis for the inhibition of Drosophila eye development by Antennapedia

Hox genes encoding homeodomain transcriptional regulators are known to spec ify the body plan of multicellular organisms and are able to induce body pl an transformations when misexpressed. These findings led to the hypothesis that duplication events and misexpression of Hox genes during evolution hav e been necessary for generating the observed morphological diversity found in metazoans. It is known that overexpressing Antennapedia (Antp) in the he ad induces antenna-to-leg as well as head-to-thorax transformation and eye reduction. At present, little is known about the exact molecular mechanism causing these phenotypes. The aim of this study is to understand the basis of inhibition of eye development. We demonstrate that Antp represses the ac tivity of the eye regulatory cascade. By ectopic expression, we show that A ntp antagonizes the activity of the eye selector gene eyeless. Using both i n vitro and in vivo experiments, we demonstrate that this inhibitory mechan ism involves direct protein-protein interactions between the DNA-binding do mains of EY and ANTP, resulting in mutual inhibition.