Hox gene Abdominal-B uses Doublesex F as a cofactor to promote neuroblast apoptosis in Drosophila central nervous system

Highly conserved DM domain containing transcription factors (Doublesex/MAB-3/DMRT1) are responsible for generating sexually dimorphic features. In CNS a set of Doublesex (Dsx) expressing neuroblasts undergo apoptosis in females while their male counterparts proliferate and give rise to serotonergic neurons crucial for adult mating behaviour. Our study demonstrates that female specific isoform of Doublesex collaborates with Hox gene Abdominal-B (AbdB) to bring about this apoptosis. Biochemical results suggest AbdB and Dsx interact through their highly conserved Homeodomain and DM domains respectively. This interaction is translated into a cooperative binding of the two proteins (AbdB and Dsx) on the apoptotic enhancer in case of females but not in case of males, resulting in female specific activation of apoptotic genes. The capacity of AbdB to utilize sex specific isoform of Dsx as a cofactor underlines the possibility that two classes of proteins are capable of cooperating in selection and regulation of target genes in tissue and sex specific manner. We propose that this interaction could be a common theme in generating sexual dimorphism in different tissues across different species.