A bZIP protein, sisterless-a, collaborates with bHLH transcription factors early in Drosophila development to determine sex.

Sexual identity in Drosophila is determined by zygotic X-chromosome dose. Two potent indicators of X-chromosome dose are sisterless-a (sis-a) and sisterless-b (sis-b). Genetic analysis has shown that a diplo-X dose of these genes activates their regulatory target, the feminizing switch gene Sex-lethal (Sxl), whereas a haplo-X dose leaves Sxl inactive. sis-b encodes a transcriptional activator of the bHLH family that dimerizes with several other HLH proteins required for the proper assessment of X dose. Here, we report that sis-a encodes a bZIP protein homolog that functions in all somatic nuclei to activate Sxl transcription. In contrast with other elements of the sex-determination signal, the functioning of this transcription factor in somatic cells may be specific to X-chromosome counting. Using in situ hybridization, we determined the time course of sis-a, sis-b, and Sxl transcription during the first few hours after fertilization. The pattern of sis-a RNA accumulation is very similar to that for sis-b, with a peak in nuclear cycle 12 at about the time of onset of Sxl transcription. Considered in the context of other studies, these results suggest that the ability to distinguish one X from two is attributable to combinatorial interactions between bZIP and bHLH proteins and their target, Sxl, as well as to positive and negative interactions with maternally supplied and zygotically produced proteins.