Mechanisms of retinal photoreceptor 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，我们使用小鼠条件性基因切除，表明转录因子Otx 2对于视网膜光感受器细胞命运决定和松果体发育至关重要。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。

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.