Transdifferentiation of the retinal pigment epithelia to the neural retina by transfer of the Pax6 transcriptional factor

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

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48 Citations (Scopus)

Abstract

The Pax6 gene plays an important role in eye morphogenesis throughout the animal kingdom. The Pax6 gene and its homologue could form ectopic eyes by targeted expression in Drosophila and Xenopus. Thus, this gene is a master gene for the eye morphogenesis at least in these animals. In the early development of the vertebrate eye, Pax6 is required for the instruction of multipotential progenitor cells of the neural retina (NR). Primitive retinal pigment epithelial (RPE) cells are able to switch their phenotype and differentiate into NR under exogenous intervention, including treatment with fibroblast growth factors (FGFs), and surgical removal of endogenous NR. However, the molecular basis of phenotypic switching is still controversial. Here, we show that Pax6 alone is sufficient to induce transdifferentiation of ectopic NR from RPE cells without addition of FGFs or surgical manipulation. Pax6-mediated transdifferentiation can be induced even at later stages of development. Both in vivo and in vitro studies show that the Pax6 lies downstream of FGF signaling, highlighting the central roles of Pax6 in NR transdifferentiation. Our results provide an evidence of retinogenic potential of nearly mature RPE and a cue for new therapeutic approaches to regenerate functional NR in patients with a visual loss.

Original languageEnglish
Pages (from-to)1059-1068
Number of pages10
JournalHuman molecular genetics
Volume14
Issue number8
DOIs
Publication statusPublished - 2005 Apr 15
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Azuma, N., Tadokoro, K., Asaka, A., Yamada, M., Yamaguchi, Y., Handa, H., Matsushima, S., Watanabe, T., Kida, Y., Ogura, T., Torii, M., Shimamura, K., & Nakafuku, M. (2005). Transdifferentiation of the retinal pigment epithelia to the neural retina by transfer of the Pax6 transcriptional factor. Human molecular genetics, 14(8), 1059-1068. https://doi.org/10.1093/hmg/ddi098