School of Life Sciences and Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 South Maryland Parkway, Box 454004, Las Vegas, NV 89154, United States.
School of Life Sciences and Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, 4505 South Maryland Parkway, Box 454004, Las Vegas, NV 89154, United States.
Exp Eye Res. 2018 Apr;169:38-47. doi: 10.1016/j.exer.2018.01.007. Epub 2018 Jan 31.
Vertebrate eye development is complex and requires early interactions between neuroectoderm and surface ectoderm during embryogenesis. In the African clawed frog, Xenopus laevis, individual eye tissues such as the retina and lens can undergo regeneration. However, it has been reported that removal of either the specified eye field at the neurula stage or the eye during tadpole stage does not induce replacement. Here we describe a model for investigating Xenopus developmental eye repair. We found that tailbud embryos can readily regrow eyes after surgical removal of over 83% of the specified eye and lens tissues. The regrown eye reached a comparable size to the contralateral control by 5 days and overall animal development was normal. It contained the expected complement of eye cell types (including the pigmented epithelium, retina and lens), and is connected to the brain. Our data also demonstrate that apoptosis, an early mechanism that regulates appendage regeneration, is also required for eye regrowth. Treatment with apoptosis inhibitors (M50054 or NS3694) blocked eye regrowth by inhibiting caspase activation. Together, our findings indicate that frog embryos can undergo successful eye repair after considerable tissue loss and reveals a required role for apoptosis in this process. Furthermore, this Xenopus model allows for rapid comparisons of productive eye repair and developmental pathways. It can also facilitate the molecular dissection of signaling mechanisms necessary for initiating repair.
脊椎动物眼睛的发育过程非常复杂，需要在胚胎发生过程中神经外胚层和表面外胚层之间进行早期的相互作用。在非洲爪蟾（Xenopus laevis）中，视网膜和晶状体等单个眼组织可以再生。然而，据报道，在神经胚期去除特定的眼区或在蝌蚪期去除眼睛并不能诱导替代。在这里，我们描述了一种用于研究非洲爪蟾发育性眼修复的模型。我们发现，尾芽胚胎在手术切除超过 83%的特定眼和晶状体组织后，可以很容易地重新长出眼睛。在 5 天时，再生的眼睛大小与对侧对照相当，整体动物发育正常。它包含了预期的眼细胞类型（包括色素上皮、视网膜和晶状体），并与大脑相连。我们的数据还表明，细胞凋亡，一种调节附肢再生的早期机制，也需要用于眼再生。用细胞凋亡抑制剂（M50054 或 NS3694）处理可通过抑制半胱天冬酶激活来阻止眼睛再生。总之，我们的发现表明，青蛙胚胎在大量组织丢失后可以进行成功的眼部修复，并揭示了细胞凋亡在这个过程中的重要作用。此外，这种非洲爪蟾模型允许对有效的眼部修复和发育途径进行快速比较。它还可以促进对启动修复所需的信号机制的分子剖析。
