A Drosophila RNAi library modulates Hippo pathway-dependent tissue growth

Nat Commun. 2016 Jan 13:7:10368. doi: 10.1038/ncomms10368.

Abstract

Libraries of transgenic Drosophila melanogaster carrying RNA interference (RNAi) constructs have been used extensively to perform large-scale functional genetic screens in vivo. For example, RNAi screens have facilitated the discovery of multiple components of the Hippo pathway, an evolutionarily conserved growth-regulatory network. Here we investigate an important technical limitation with the widely used VDRC KK RNAi collection. We find that approximately 25% of VDRC KK RNAi lines cause false-positive enhancement of the Hippo pathway, owing to ectopic expression of the Tiptop transcription factor. Of relevance to the broader Drosophila community, ectopic tiptop (tio) expression can also cause organ malformations and mask phenotypes such as organ overgrowth. To enhance the use of the VDRC KK RNAi library, we have generated a D. melanogaster strain that will allow researchers to test, in a single cross, whether their genetic screen of interest will be affected by ectopic tio expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Ectopic Gene Expression
  • Female
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Nuclear Proteins / metabolism
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Interference*
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*
  • YAP-Signaling Proteins

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • YAP-Signaling Proteins
  • Yki protein, Drosophila
  • tio protein, Drosophila
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila