Save Sight Institute and Anatomy & Histology, Bosch Institute, The University of Sydney, NSW 2006, Australia.
Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Australia.
Exp Eye Res. 2018 May;170:58-66. doi: 10.1016/j.exer.2018.02.012. Epub 2018 Feb 16.
The development and growth of the vertebrate ocular lens is dependent on the regulated proliferation of an anterior monolayer of epithelial cells, and their subsequent differentiation into elongate fiber cells. The growth factor rich ocular media that bathes the lens mediates these cellular processes, and their respective intracellular signaling pathways are in turn regulated to ensure that the proper lens architecture is maintained. Recent studies have proposed that Cysteine Rich Motor Neuron 1 (Crim1), a transmembrane protein involved in organogenesis of many tissues, might influence cell adhesion, polarity and proliferation in the lens by regulating integrin-signaling. Here, we characterise the lens and eyes of the Crim1 mutant mice, and show that the loss of Crim1 function in the ocular tissues results in inappropriate differentiation of the lens epithelium into fiber cells. Furthermore, restoration of Crim1 levels in just the lens tissue of Crim1 mice is sufficient to ameliorate most of the dysgenesis observed in the mutant animals. Based on our findings, we propose that tight regulation of Crim1 activity is required for maintenance of the lens epithelium, and its depletion leads to ectopic differentiation into fiber cells, dramatically altering lens structure and ultimately leading to microphthalmia and aphakia.
脊椎动物眼球晶状体的发育和生长依赖于前部单层上皮细胞的调节性增殖，以及它们随后分化成长纤维细胞。富含生长因子的眼球介质（baths the lens）介导了这些细胞过程，而它们各自的细胞内信号通路则受到调节，以确保维持适当的晶状体结构。最近的研究表明，参与许多组织器官发生的跨膜蛋白胱氨酸丰富运动神经元 1（Cysteine Rich Motor Neuron 1，Crim1）可能通过调节整合素信号影响晶状体中的细胞黏附、极性和增殖。在这里，我们对 Crim1 突变小鼠的晶状体和眼睛进行了特征描述，结果表明，眼部组织中 Crim1 功能的丧失导致晶状体上皮细胞异常分化为纤维细胞。此外，仅在 Crim1 小鼠的晶状体组织中恢复 Crim1 水平足以改善突变动物中观察到的大多数发育不良。基于我们的发现，我们提出 Crim1 活性的严格调节对于维持晶状体上皮细胞是必需的，其耗竭会导致纤维细胞的异位分化，从而显著改变晶状体结构，并最终导致小眼和无晶状体。
