Generation of a sexually dimorphic neuronal population in Drosophila

Differences in the number, morphology and function of neurons between the sexes underlie sexually dimorphic behaviours and physiology. In Drosophila, neuronal sexual dimorphism is determined by the sex determination cascade, most of which occurs downstream of Transformer (Tra). Tra is only expressed in females where it splices the sex determination effectors, fruitless (fru) and doublesex (dsx), into female-specific isoforms (non-coding fruF and coding dsxF transcripts). In males, Tra is not expressed, which leads to default splicing of fru and dsx into male-specific isoforms (coding fruM and dsxM transcripts). Sex-specific isoforms of Fru and Dsx direct most, if not all, sex differences during development of the nervous system. The development of the male nervous system has been well-studied, whereas the mechanisms that give rise to female-specific dimorphisms have been less researched. We used a subset of insulin-like peptide 7 (Ilp7)-expressing neurons as a model for studying the development of neuronal sex differences. These neurons express fru but not dsx, and innervate the reproductive organs. Using a genetic approach, we found novel roles for tra and fru in generating a female-specific ventral subset of Ilp7 neurons (FS-Ilp7 neurons). We found FruM-dependent male-specific programmed cell death (PCD) of FS-Ilp7 neurons underlies their female-specific generation. Furthermore, we found that FruM is necessary for serotonergic differentiation and for proper axonal targeting of Ilp7 neurons in males. In females, we show that forcing male-specific splicing of fru is insufficient to trigger PCD, because, unexpectedly, Tra prevents FruM-dependent PCD in two ways to ensure FS-Ilp7 neuronal survival; not only does Tra act canonically in fru splicing, but it also acts non-canonically in parallel or downstream of fru splicing to block fruM-dependent PCD. We conclude that FruM controls both neuronal numbers via PCD and arborization in post-embryonic Ilp7 neurons, and that Tra plays a novel failsafe function in females to establish and then reinforce the decision to generate female-specific neurons.Medicine, Faculty ofGraduat