A Search for Genes Mediating the Growth-Promoting Function of TGFβ in the Drosophila melanogaster Wing Disc

Genetics. 2017 May;206(1):231-249. doi: 10.1534/genetics.116.197228. Epub 2017 Mar 17.

Abstract

Transforming Growth Factor β (TGFβ) signaling has a complex influence on cell proliferation, acting to stop cell division in differentiating cells, but also promoting cell division in immature cells. The activity of the pathway in Drosophila is mostly required to stimulate the proliferation of neural and epithelial tissues. Most interestingly, this function is not absolutely required for cell division, but it is needed for these tissues to reach their correct size. It is not known how TGFβ signaling promotes cell division in imaginal discs, or what the interactions between TGFβ activity and other signaling pathways regulating cell proliferation are. In this work, we have explored the disc autonomous function of TGFβ that promotes wing imaginal disc growth. We have studied the genetic interactions between TGFβ signaling and other pathways regulating wing disc growth, such as the Insulin and Hippo/Salvador/Warts pathways, as well as cell cycle regulators. We have also identified a collection of TGFβ candidate target genes affecting imaginal growth using expression profiles. These candidates correspond to genes participating in the regulation of a variety of biochemical processes, including different aspects of cell metabolism, suggesting that TGFβ could affect cell proliferation by regulating the metabolic fitness of imaginal cells.

Keywords: Smad2; TGFβ; growth control; imaginal disc; microarray analysis.

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics*
  • Cell Division / genetics
  • Cell Proliferation / genetics
  • Cell Size
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Gene Expression Regulation, Developmental
  • Genetic Fitness
  • Imaginal Discs / growth & development
  • Insulin / genetics
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Protein Kinases / genetics*
  • Protein Serine-Threonine Kinases / genetics*
  • Signal Transduction
  • Transcriptome
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics*
  • Wings, Animal / growth & development

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Insulin
  • Intracellular Signaling Peptides and Proteins
  • Transforming Growth Factor beta
  • sav protein, Drosophila
  • Protein Kinases
  • wts protein, Drosophila
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila