Topology-driven protein-protein interaction network analysis detects genetic sub-networks regulating reproductive capacity

Elife. 2020 Sep 9;9:e54082. doi: 10.7554/eLife.54082.


Understanding the genetic regulation of organ structure is a fundamental problem in developmental biology. Here, we use egg-producing structures of insect ovaries, called ovarioles, to deduce systems-level gene regulatory relationships from quantitative functional genetic analysis. We previously showed that Hippo signalling, a conserved regulator of animal organ size, regulates ovariole number in Drosophila melanogaster. To comprehensively determine how Hippo signalling interacts with other pathways in this regulation, we screened all known signalling pathway genes, and identified Hpo-dependent and Hpo-independent signalling requirements. Network analysis of known protein-protein interactions among screen results identified independent gene regulatory sub-networks regulating one or both of ovariole number and egg laying. These sub-networks predict involvement of previously uncharacterised genes with higher accuracy than the original candidate screen. This shows that network analysis combining functional genetic and large-scale interaction data can predict function of novel genes regulating development.

Keywords: D. melanogaster; Hippo signalling; computational biology; developmental biology; interactome; network analysis; ovariole; ovary; reproduction; systems biology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Drosophila Proteins / physiology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Female
  • Gene Regulatory Networks / physiology*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Male
  • Oviposition / genetics*
  • Protein Interaction Maps*
  • Protein Serine-Threonine Kinases / physiology
  • Signal Transduction / genetics


  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila