Homeotic function of Drosophila Bithorax-complex miRNAs mediates fertility by restricting multiple Hox genes and TALE cofactors in the CNS

Dev Cell. 2014 Jun 23;29(6):635-48. doi: 10.1016/j.devcel.2014.04.023. Epub 2014 Jun 5.

Abstract

The Drosophila Bithorax complex (BX-C) Hox cluster contains a bidirectionally transcribed miRNA locus, and a deletion mutant (Δmir) 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. Δmir 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 Δmir mutants was substantially rescued by heterozygosity of these genes. The posterior VNC contains Ilp7+ oviduct motoneurons, whose innervation and morphology are defective in Δmir females, and substantially rescued by heterozygosity of Δmir 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Body Patterning
  • Central Nervous System / cytology
  • Central Nervous System / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Female
  • Gene Expression Regulation, Developmental* / physiology
  • Genes, Homeobox / physiology
  • Homeodomain Proteins / genetics*
  • Image Processing, Computer-Assisted
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Larva / growth & development
  • Larva / metabolism*
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Motor Neurons / cytology
  • Motor Neurons / metabolism
  • Multigene Family
  • Oviducts / cytology
  • Oviducts / metabolism*
  • Sequence Homology, Nucleic Acid
  • Sexual Behavior, Animal
  • Transcription Factors / genetics

Substances

  • Drosophila Proteins
  • Homeodomain Proteins
  • MicroRNAs
  • Transcription Factors
  • achi protein, Drosophila