Mechanisms of retinal photoreceptor development

视网膜感光器发育机制

• 批准号: 14380356
• 负责人: FURUKAWA Takahisa
• 金额: $ 9.66万
• 依托单位: Osaka Bioscience Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14380356/
• 关键词: retina; photoreceptor cell; gene; retinal item cell; retinal degeneration; pineal gland; neuronal regeneration; trasinjection factor; 中枢神経系; 細胞運命; 光受容体; 遺伝子制御

Understanding the molecular mechanisms by which distinct cell fate is determined during organogenesis is a central issue in development and disease. Here, using conditional gene ablation in mice, we show that the transcription factor Otx2 is essential for retinal photoreceptor cell fate determination and development of the pineal gland. Otx2-deficiency converted differentiating photoreceptor cells to amacrine-like neurons and led to total lack of pinealocytes in the pineal gland. We also found that Otx2 transactivates the cone-rod homeobox gene, Crx, which is required for terminal differentiation and maintenance of photoreceptor cells. Furthermore, retroviral gene transfer of Otx2 steers retinal progenitor cells toward becoming photoreceptors. Thus, Otx2 is a key regulatory gene for the cell fate determination of retinal photoreceptor cells. Our results reveal the key molecular steps required for photoreceptor cell-fate determination and pinealocyte development.

了解器官发生过程中决定不同细胞命运的分子机制是发育和疾病的核心问题。在这里，使用条件基因消融小鼠，我们表明，转录因子Otx2是必不可少的视网膜感光细胞的命运决定和发展的松果体。Otx2缺陷将分化中的感光细胞转化为无长突样神经元，并导致松果体中完全缺乏松果体细胞。我们还发现，Otx2反式激活锥杆同源盒基因，Crx，这是所需的终末分化和维持感光细胞。此外，逆转录病毒基因转移的Otx2转向视网膜祖细胞成为光感受器。因此，Otx2是决定视网膜感光细胞命运的关键调控基因。我们的研究结果揭示了感光细胞命运决定和松果体细胞发育所需的关键分子步骤。

项目成果

Nishida, A., Furukawa, A., Koike, C., Tano, Y., Aizawa, S., Matsuo, I., Furukawa, T.: "Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development"Nature Neuroscience. 6. 1255-1263 (2003)

Nishida, A.、Furukawa, A.、Koike, C.、Tano, Y.、Aizawa, S.、Matsuo, I.、Furukawa, T.：“Otx2 同源盒基因控制视网膜感光细胞命运和松果体发育”《自然》

Nishida, A: "Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development"Nature Neuroscience. 6・12. 1255-1263 (2003)

Nishida, A：“Otx2 同源盒基因控制视网膜感光细胞命运和松果体发育”《自然神经科学》6·12 1255-1263（2003）。

Nishida, A: "Otx2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development"Nature Neuroscience. 6. 1255-1263 (2003)

Nishida, A：“Otx2 同源框基因控制视网膜感光细胞命运和松果体发育”《自然神经科学》。

Furukawa, A: "The mouse Crx5' upstream transgene sequence directs a cell-specific and developmentally regulated expression in retinal photoreceptor cells"J of Neuroscience. 22・7. 1640-1647 (2002)

Furukawa, A：“小鼠 Crx5 上游转基因序列指导视网膜感光细胞中的细胞特异性和发育调节表达”J of Neuroscience 22·7 (2002)。