Sex determination in Drosophila: The view from the top

One of the most important decisions in development is whether to be male or female. In Drosophila melanogaster, most cells make this choice independent of their neighbors such that diploid cells with one X chromosome (XY) are male and those with two X chromosomes (XX) are female. X-chromosome number is relayed through regulatory proteins that act together to activate Sex-lethal (Sxl) in XX animals. The resulting SXL female specific RNA binding protein modulates the expression of a set of downstream genes, ultimately leading to sexually dimorphic structures and behaviors. Despite the apparent simplicity of this mechanism, Sxl activity is controlled by a host of transcriptional and posttranscriptional mechanisms that tailor its function to specific developmental scenarios. This review describes recent advances in our understanding of Sxl regulation and function, highlighting work that challenges some of the textbook views about this classical (often cited, yet poorly understood) binary switch gene.