PATTERNING OF THE DROSOPHILA EMBRYO BY A HOMEODOMAIN-DELETED FTZ POLYPEPTIDE

HOMEODOMAIN proteins regulate diverse developmental processes in a wid e range of organisms, yet bind in vitro to DNA sequences that are rema rkably similar(1). This has raised the fundamental question of how tar get gene specificity is achieved in vivo. The Drosophila fushi tarazu protein (Ftz) contains a homeodomain(2) and is required for the format ion of alternate segments(3). We have shown previously that a homeodom ain-deleted Ftz polypeptide (Ftz Delta HD), incapable of binding DNA i n vitro, could regulate endogenous ftz gene expression(4). Here we tes t Ftz Delta HD activities in a ftz mutant background and find that, su rprisingly, Ftz Delta HD can directly regulate ftz-dependent segmentat ion, suggesting that it can control target gene expression through int eractions with other proteins. A likely candidate is the pair-rule pro tein Paired (Prd). Ftz Delta HD bound directly to Prd in vitro and req uired Prd to repress wingless in vivo. These results emphasize the piv otal importance of protein-protein interactions in homeodomain protein function.