Drosophila female-specific Ilp7 motoneurons are generated by Fruitless-dependent cell death in males and by 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 Fru^MC isoform. However, in females, fru alleles that only generate Fru^M isoforms failed to kill FS-Ilp7 motoneurons. This blockade of Fru^M-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 that regulates female-specific splicing of fru and dsx transcripts. In both sexes, we show that Tra prevents PCD even when the Fru^M isoform is expressed. In addition, we found that Fru^MC eliminated FS-Ilp7 motoneurons in both sexes, but only when Tra was absent. Thus, Fru^MC-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.

Keywords: Insulin-like peptide 7; Motoneuron development; Programmed cell death; Sex determination; Sexual dimorphism.