Homeotic Function of Drosophila Bithorax-Complex miRNAs Mediates Fertility by Restricting Multiple Hox Genes and TALE Cofactors in the CNS

The Drosophila Bithorax complex (BX-C) Hox cluster contains a bidirectionally transcribed miRNA locus, and a deletion mutant (Delta mir) lays no eggs and is completely sterile. We show these miRNAs are expressed and active in distinct spatial registers along the anterior-posterior axis in the CNS. Delta mir larvae derepress a network of direct homeobox gene targets in the posterior ventral nerve cord (VNC), including BX-C genes and their TALE cofactors. These are phenotypically critical targets, because sterility of Delta mir mutants was substantially rescued by heterozygosity of these genes. The posterior VNC contains IIp7+ oviduct motoneurons, whose innervation and morphology are defective in Delta mir females, and substantially rescued by heterozygosity of Delta mir targets, especially within the BX-C. Collectively, we reveal (1) critical roles for Hox miRNAs that determine segment-specific expression of homeotic genes, which are not masked by transcriptional regulation; and (2) that BX-C miRNAs are essential for neural patterning and reproductive behavior.