The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors

Nuclear hormone receptors and homeodomain proteins are two classes of transcription factor that regulate major developmental processes. Both depend on interactions with other proteins for specificity and activity. The Drosophila gene fushi tarazu (ftz), which encodes a homeodomain protein(1) (Ftz), is required zygotically for the formation of alternate segments in the developing embryo(2). Here we show that the orphan nuclear receptor alpha Ftz-F1 (ref. 3), which is deposited in the egg during oogenesis(4), is an obligatory cofactor for Ftz. The two proteins interact specifically and directly, both in vitro and in vivo, through a conserved domain in the Ftz polypeptide. This interaction suggests that other nuclear receptor/homeodomain protein interactions may be important and common in developing organisms.