The Drosophila segmentation gene runt acts as a position-specific numerator element necessary for the uniform expression of the sex-determining gene Sex-lethal.

Female development in Drosophila is established through the activation of the X:A target gene Sex-lethal (Sxl) by an X:A ratio of 1. X-linked zygotic genes, termed numerator elements, comprise part of the X:A ratio and are primarily responsible for the activation of Sxl in females. We demonstrate that the X-linked segmentation gene runt is required for this process and has genetic and molecular properties of a numerator element. Genetically, runt has vital dose-dependent interactions with components of the X:A ratio and alterations in runt activity alter the sexual phenotype of triploid intersexes. Molecularly, loss of runt activity results in a failure to activate appropriately Sxl in the central region of female embryos. We also show that Sxl activation is influenced by the maternal anterior and terminal pattern-forming genes, bicoid (bcd) and torso (tor). These results indicate that the "uniform" activation of Sxl requires input from nonuniformly distributed products. We have demonstrated that runt is one such product and suggest that other genes with nonuniform input exist. runt is distinguished from previously identified regulators of Sxl by its nonuniform role and by the absence of an identifiable helix-loop-helix (HLH) motif, indicating that the activation of Sxl is not controlled solely by HLH proteins.