Erect wing regulates synaptic growth in Drosophila by integration of multiple signaling pathways

Genome Biol. 2008 Apr 17;9(4):R73. doi: 10.1186/gb-2008-9-4-r73.


Background: Formation of synaptic connections is a dynamic and highly regulated process. Little is known about the gene networks that regulate synaptic growth and how they balance stimulatory and restrictive signals.

Results: Here we show that the neuronally expressed transcription factor gene erect wing (ewg) is a major target of the RNA binding protein ELAV and that EWG restricts synaptic growth at neuromuscular junctions. Using a functional genomics approach we demonstrate that EWG acts primarily through increasing mRNA levels of genes involved in transcriptional and post-transcriptional regulation of gene expression, while genes at the end of the regulatory expression hierarchy (effector genes) represent only a minor portion, indicating an extensive regulatory network. Among EWG-regulated genes are components of Wingless and Notch signaling pathways. In a clonal analysis we demonstrate that EWG genetically interacts with Wingless and Notch, and also with TGF-beta and AP-1 pathways in the regulation of synaptic growth.

Conclusion: Our results show that EWG restricts synaptic growth by integrating multiple cellular signaling pathways into an extensive regulatory gene expression network.

Publication types

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

MeSH terms

  • Animals
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • ELAV Proteins
  • Gene Expression Regulation*
  • Gene Regulatory Networks*
  • Neurons
  • Neuropeptides / physiology*
  • Receptors, Notch / genetics
  • Signal Transduction*
  • Synapses / ultrastructure*
  • Transcription Factor AP-1 / genetics
  • Transcription Factors / physiology*
  • Transforming Growth Factor beta / genetics
  • Wnt1 Protein / genetics


  • Drosophila Proteins
  • ELAV Proteins
  • EWG protein, Drosophila
  • Neuropeptides
  • Receptors, Notch
  • Transcription Factor AP-1
  • Transcription Factors
  • Transforming Growth Factor beta
  • Wnt1 Protein
  • wg protein, Drosophila