Mechanisms of Retinal Photoreceptor differentiation

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18590090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Osaka Bioscience Institute
• Principal Investigator: KOIKE Chieko Osaka Bioscience Institute, Research associate (80342723)
• Project Period (FY): 2006 – 2007
• Keywords: Photoreceptor / Crx / transcription / retina / promoter / silencer / pineal gland / homeobox

Research Abstract

We previously reported that Crx, an otx-like homeobox gene, is a major regulator of various photoreceptor-specific genes, as well as key enzymes for meIatonin synthesis. We also found that mutation of human CRX are associated with three types of photoreceptor diseases. We also reported that Otx2 is the regulator of Crx expression and essential for photoreceptor cell fate determination.
We have studies the cooperative effect of Otx2 and Crx in the retinal development. We first examined the roles of Otx2 in the terminal differentiation of photoreceptors by analyzing Otx2; Crx double-knockout mice. In Otx2+/-; Crx-/- retinas, photoreceptor degeneration and downregulation of photoreceptor-specific genes were much more prominent than in Crx-/-retinas, suggesting that Otx2 has a role in the terminal differentiation of the photoreceptors. Moreover, bipolar cells decreased in the Otx2+/-; Crx-/- retina, suggesting that Otx2 is also involved in retinal bipolar-cell development. To further investigate the role of Otx2 in bipolar-cell development, we generated a postnatal bipolar-cell-specific Otx2 conditional-knockout mouse line. Immunohistochemical analysis of this line showed that the expression of protein kinase C, a marker of mature bipolar cells, was significantly downregulated in the retina. Electroretinograms revealed that the electrophysiological function of retinal bipolar cells was impaired as a result of Otx2 ablation. These data suggest that Otx2 plays a functional role in the maturation of retinal photoreceptor and bipolar cells. We reported these results in Molecular and Cellular Biology (27 p 8318-8329, 2007).

Research Products

• [Journal Article] 網膜視細胞の細胞極性と細胞内オルガネラの制御 -外節形成、繊毛内輸送、核のポジショニングから網膜変性症まで- (2008)
  • Author(s): 小池千恵子、古川貴久
  • Journal Title: 生化学 80 Pages: 224-232
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Regulation of cell polarity and intracellular organelles in retinal photoreceptor cells (2008)
  • Author(s): Chieko Koike, Takahisa Furukawa
  • Journal Title: Seikagaku 80 Pages: p224-232
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Functional roles of Otx2 transcription factor in postnatal mouse retinal development (2007)
  • Author(s): Koike C,Nishida A,Ueno S,Saito H,Sanuki R,Sato S,Furukawa A,Aizawa S,Matsuo I,Suzuki N,Kondo M,Furukawa T
  • Journal Title: Mol Cell Biol 27 Pages: 8318-8329
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Functional roles of Otx2 transcription factor in postnatal mouse retinal development (2007)
  • Author(s): Koike C, Nishida A, Ueno S, Saito H, Sanuki R, Sato S, Furukawa A, Aizawa S, Matsuo I, Suzuki N, Kondo M, Furukawa T
  • Journal Title: Mol. Cell., Biol. 27 Pages: p8318-8329
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cloning and characterization of mr-s, a novel SAM domain protein, predominantly expressed in retinal photoreceptor cells (2006)
  • Author(s): Inoue T,Terada K,Furukawa A,Koike C,Tamaki Y,Araie M,Furukawa T.
  • Journal Title: BMC Developmental Biology 6 Pages: 15
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Cloning and characterization of mr-s, a novel SAM domain protein, predominantly expressed in retinal photoreceptor cells (2006)
  • Author(s): Inoue T, Terada K. Furukawa A, Koike C, Tamaki Y, Araie M, Furukawa T.
  • Journal Title: BMC Developmental Biology 6 Pages: 15
  • Description: 「研究成果報告書概要(欧文)」より