Males and females: Creating differences while maintaining the similarities

During metazoan development, a small number of signaling pathways are iteratively used to orchestrate diverse processes such as cell division, cell fate specification and survival. Temporal and spatial regulation of these pathways underlies the final cellular makeup, size and shape of organs. In Drosophila melanogaster, the master switch gene Sex-lethal (Sxl) orchestrates all aspects of female development and behavior by modulating gene expression. Many of the sex-specific differences in gene expression and morphology are controlled through a gene activity cascade that involves Sxl→tra→dsx-fru. However, various aspects of somatic sexual development appear to be independent of this cascade. Consistent with this idea, Sxl protein, on its own, was recently implicated in the regulation of both Hh and Notch signaling to shape some of the sexually dimorphic traits. Paradoxically, however, Sxl activity is essential in every female cell to prevent the activation of the male-specific dosage compensation system and thus to ensure the proper level of X-linked gene expression. This raises a key question as to how the sex-specific effects of Sxl on major signaling pathways are prevented in monomorphic tissues during female development. We have elucidated a novel mechanism where Hrp48, an abundant essential hnRNP functions to restrict Sxl expression in monomrphic tissues and thus allow for proper development. Our findings bring into focus the critical role played by general homeostatic factors in specification of diverse cell fates and morphogenesis.