The Pax6 isoform bearing an alternative spliced exon promotes the development of the neural retinal structure

Hum Mol Genet. 2005 Mar 15;14(6):735-45. doi: 10.1093/hmg/ddi069. Epub 2005 Jan 27.


The vertebrate retina has an area where visual cells are closely packed for proper vision that is known as a fovea, an area centralis or a visual streak. The molecular mechanism that regulates the formation of these structures and visual cell gradients is unknown. The transcription factor Pax6 is a master regulator of eye development. A Pax6 isoform that contains an exon 5a-encoded 14 amino acid insertion in its paired domain, Pax6(+5a), has different DNA-binding properties compared with the Pax6(-5a) isoform. Little is known about the functional significance of Pax6(+5a). Here, we show that Pax6(+5a) is expressed especially in the retinal portion where visual cells accumulate during eye development and, when overexpressed, induces a remarkable well-differentiated retina-like structure. Pax6(+5a) proteins that bear point mutations that are found in patients with foveal hypoplasia are unable to induce these ectopic retina-like structures. We propose that Pax6(+5a) induces a developmental cascade in the prospective fovea, area centralis or visual streak region that leads to the formation of a retinal architecture bearing densely packed visual cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / physiology*
  • Amino Acid Substitution / genetics
  • Animals
  • Chick Embryo
  • Chickens
  • Exons / genetics
  • Eye Proteins / biosynthesis*
  • Eye Proteins / genetics
  • Fovea Centralis / embryology*
  • Gene Expression Regulation, Developmental / physiology*
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Humans
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Point Mutation
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / genetics


  • Eye Proteins
  • Homeodomain Proteins
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Protein Isoforms
  • Repressor Proteins