Drosophila female-specific Ilp7 motoneurons are generated by Fruitless-dependent cell death in males and a double-assurance survival role for Transformer in females

Abstract

Female-specific Ilp7 neuropeptide-expressing motoneurons (FS-Ilp7 motoneurons) are required in Drosophila for oviduct function in egg-laying. Here, we uncover cellular and genetic mechanisms underlying their female-specific generation. We demonstrate that programmed cell death (PCD) eliminates FS-Ilp7 motoneurons in males, and that this requires male-specific splicing of the sex determination gene fruitless (fru) into the FruMC isoform. However, in females, fru alleles that only generate FruM isoforms failed to kill FS-Ilp7 motoneurons. This blockade of FruM-dependent PCD was not attributable to doublesex gene function but to a non-canonical role for transformer (tra), a gene encoding the RNA splicing activator of fru and dsx gene transcripts that is only functional in females and prevents splicing into the FruM protein isoform. However, in both sexes, we show that Tra prevents PCD even in the presence of constitutive FruM isoform generation. In addition, we found that FruMC eliminated FS-Ilp7 motoneurons in both sexes, but only when Tra is absent. Thus, FruMC-dependent PCD eliminates female-specific neurons in males, and Tra plays a double-assurance function in females to establish and reinforce the decision to generate female-specific neurons.