A Wingless and Notch double-repression mechanism regulates G1-S transition in the Drosophila wing

EMBO J. 2008 Jun 4;27(11):1633-45. doi: 10.1038/emboj.2008.84. Epub 2008 May 1.

Abstract

The control of tissue growth and patterning is orchestrated in various multicellular tissues by the coordinated activity of the signalling molecules Wnt/Wingless (Wg) and Notch, and mutations in these pathways can cause cancer. The role of these molecules in the control of cell proliferation and the crosstalk between their corresponding pathways remain poorly understood. Crosstalk between Notch and Wg has been proposed to organize pattern and growth in the Drosophila wing primordium. Here we report that Wg and Notch act in a surprisingly linear pathway to control G1-S progression. We present evidence that these molecules exert their function by regulating the expression of the dmyc proto-oncogene and the bantam micro-RNA, which positively modulated the activity of the E2F transcription factor. Our results demonstrate that Notch acts in this cellular context as a repressor of cell-cycle progression and Wg has a permissive role in alleviating Notch-mediated repression of G1-S progression in wing cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism
  • G1 Phase*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Receptors, Notch / metabolism*
  • Repressor Proteins / metabolism*
  • S Phase*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Wings, Animal / cytology
  • Wings, Animal / growth & development*
  • Wings, Animal / metabolism
  • Wnt1 Protein

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • MicroRNAs
  • Myc protein, Drosophila
  • N protein, Drosophila
  • Proto-Oncogene Proteins
  • Receptors, Notch
  • Repressor Proteins
  • Transcription Factors
  • Wnt1 Protein
  • bantam microRNA, Drosophila
  • wg protein, Drosophila