Drosophila growth and development in the absence of dMyc and dMnt

Dev Biol. 2008 Mar 15;315(2):303-16. doi: 10.1016/j.ydbio.2007.12.026. Epub 2007 Dec 27.

Abstract

Myc oncoproteins are essential regulators of the growth and proliferation of mammalian cells. In Drosophila the single ortholog of Myc (dMyc), encoded by the dm gene, influences organismal size and the growth of both mitotic and endoreplicating cells. A null mutation in dm results in attenuated endoreplication and growth arrest early in larval development. Drosophila also contains a single ortholog of the mammalian Mad/Mnt transcriptional repressor proteins (dMnt), which is thought to antagonize dMyc function. Here we show that animals lacking both dMyc and dMnt display increased viability and grow significantly larger and develop further than dMyc single mutants. We observe increased endoreplication and growth of larval tissues in these double mutants and disproportionate growth of the imaginal discs. Gene expression analysis indicates that loss of dMyc leads to decreased expression of genes required for ribosome biogenesis and protein synthesis. The additional loss of dMnt partially rescues expression of a small number of dMyc and dMnt genes that are primarily involved in rRNA synthesis and processing. Our results indicate that dMnt repression is normally overridden by dMyc activation during larval development. Therefore the severity of the dm null phenotype is likely due to unopposed repression by dMnt on a subset of genes critical for cell and organismal growth. Surprisingly, considerable growth and development can occur in the absence of both dMyc and dMnt.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / deficiency
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / physiology
  • DNA Primers / genetics
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Drosophila / genetics*
  • Drosophila / growth & development*
  • Drosophila / physiology
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / physiology
  • Female
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Genes, Insect*
  • Larva / growth & development
  • Male
  • Metamorphosis, Biological
  • Mutation*
  • Phenotype
  • Repressor Proteins / genetics*
  • Repressor Proteins / physiology
  • Signal Transduction
  • Transcription Factors / deficiency
  • Transcription Factors / genetics*
  • Transcription Factors / physiology
  • Wings, Animal / growth & development

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA Primers
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Myc protein, Drosophila
  • Repressor Proteins
  • Transcription Factors