Identification of novel elements of the Drosophila blisterome sheds light on potential pathological mechanisms of several human diseases

PLoS One. 2014 Jun 26;9(6):e101133. doi: 10.1371/journal.pone.0101133. eCollection 2014.

Abstract

Main developmental programs are highly conserved among species of the animal kingdom. Improper execution of these programs often leads to progression of various diseases and disorders. Here we focused on Drosophila wing tissue morphogenesis, a fairly complex developmental program, one of the steps of which--apposition of the dorsal and ventral wing sheets during metamorphosis--is mediated by integrins. Disruption of this apposition leads to wing blistering which serves as an easily screenable phenotype for components regulating this process. By means of RNAi-silencing technique and the blister phenotype as readout, we identify numerous novel proteins potentially involved in wing sheet adhesion. Remarkably, our results reveal not only participants of the integrin-mediated machinery, but also components of other cellular processes, e.g. cell cycle, RNA splicing, and vesicular trafficking. With the use of bioinformatics tools, these data are assembled into a large blisterome network. Analysis of human orthologues of the Drosophila blisterome components shows that many disease-related genes may contribute to cell adhesion implementation, providing hints on possible mechanisms of these human pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computational Biology
  • Drosophila / embryology*
  • Drosophila / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Molecular Sequence Annotation
  • Morphogenesis / genetics*
  • Phenotype
  • RNA Interference
  • Wings, Animal / embryology*
  • Wings, Animal / metabolism*

Grants and funding

The work was supported by the Swiss National Science Foundation (grant #31003A_138350) to V.L.K. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.