Growth and specification of the eye are controlled independently by Eyegone and Eyeless in Drosophila melanogaster

Nat Genet. 2004 Jan;36(1):31-9. doi: 10.1038/ng1281. Epub 2003 Dec 14.


Control of growth determines the size and shape of organs. Localized signals known as 'organizers' and members of the Pax family of proto-oncogenes are both elements in this control. Pax proteins have a conserved DNA-binding paired domain, which is presumed to be essential for their oncogenic activity. We present evidence that the organizing signal Notch does not promote growth in eyes of D. melanogaster through either Eyeless (Ey) or Twin of eyeless (Toy), the two Pax6 transcription factors. Instead, it acts through Eyegone (Eyg), which has a truncated paired domain, consisting of only the C-terminal subregion. In humans and mice, the sole PAX6 gene produces the isoform PAX6(5a) by alternative splicing; like Eyegone, this isoform binds DNA though the C terminus of the paired domain. Overexpression of human PAX6(5a) induces strong overgrowth in vivo, whereas the canonical PAX6 variant hardly effects growth. These results show that growth and eye specification are subject to independent control and explain hyperplasia in a new way.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning
  • DNA-Binding Proteins / physiology*
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics*
  • Eye / embryology*
  • Eye Proteins
  • Gene Expression Regulation, Developmental*
  • Genes, Insect
  • Homeodomain Proteins / physiology
  • Membrane Proteins / physiology
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Protein Isoforms / metabolism
  • Receptors, Notch
  • Repressor Proteins
  • Signal Transduction


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • Membrane Proteins
  • N protein, Drosophila
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Protein Isoforms
  • Receptors, Notch
  • Repressor Proteins
  • ey protein, Drosophila
  • eyg protein, Drosophila