A Myc-Groucho complex integrates EGF and Notch signaling to regulate neural development

Amir Orian*, Jeffrey J. Delrow, Alicia E. Rosales Nieves, Mona Abed, David Metzger, Ze'ev Paroush, Robert N. Eisenman, Susan M. Parkhurst

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Integration of patterning cues via transcriptional networks to coordinate gene expression is critical during morphogenesis and misregulated in cancer. Using DNA adenine methyltransferase (Dam)ID chromatin profiling, we identified a protein-protein interaction between the Drosophila Myc oncogene and the Groucho corepressor that regulates a subset of direct dMyc targets. Most of these shared targets affect fate or mitosis particularly during neurogenesis, suggesting the dMyc-Groucho complex may coordinate fate acquisition with mitotic capacity during development. We find an antagonistic relationship between dMyc and Groucho that mimics the antagonistic interactions found for EGF and Notch signaling: dMyc is required to specify neuronal fate and enhance neuroblast mitosis, whereas Groucho is required to maintain epithelial fate and inhibit mitosis. Our results suggest that the dMyc-Groucho complex defines a previously undescribed mechanism of Myc function and may serve as the transcriptional unit that integrates EGF and Notch inputs to regulate early neuronal development.

Original languageAmerican English
Pages (from-to)15771-15776
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number40
DOIs
StatePublished - 2 Oct 2007

Keywords

  • Cell fate
  • Drosophila
  • Mitosis
  • Neurogenesis
  • Stem cell

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