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

Noriyuki Azuma, Keiko Tadokoro, Astuko Asaka, Masao Yamada, Yuki Yamaguchi, Hiroshi Handa, Satsuki Matsushima, Takashi Watanabe, Shinichi Kohsaka, Yasuyuki Kida, Tomoki Shiraishi, Toshihiko Ogura, Kenji Shimamura, Masato Nakafuku

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)735-745
Number of pages11
JournalHuman molecular genetics
Issue number6
Publication statusPublished - 2005 Mar 15
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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