Ras-Related Nuclear Protein is required for late developmental stages of retinal cells in zebrafish eyes.
Ras-Related Nuclear Protein is required for late developmental stages of retinal cells in zebrafish eyes.
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DOI：
10.1387/ijdb.150310ht
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Cheng-Yung Lin;Hsing-Yen Huang;Po-nien Lu;Chien-Wei Lin;Kuan-Ming Lu;H. Tsai
中科院分区：
文献类型：
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作者：
Cheng-Yung Lin;Hsing-Yen Huang;Po-nien Lu;Chien-Wei Lin;Kuan-Ming Lu;H. Tsai
Ras相关核蛋白（Ran）通过调节核质转运和微管蛋白的组装参与细胞分裂。然而，它在胚胎发育中的功能尚不清楚。我们利用斑马鱼研究Ran在眼睛发育中的作用。咽期以后，ran转录本在头和眼中限制性表达。在ran缺陷的胚胎中观察到小眼球，其中没有检测到具有分化的视网膜细胞的有序层。他们表现出更快的下降cyclinD 1表达的细胞，这表明在视网膜细胞周期调控是有缺陷的。在ran缺陷的胚胎早期（24 hpf），视网膜中的凋亡信号仍然较低。早期眼野规格标记，rx 1和pax 6，只有轻微的影响，和标记建立轴突迁移，fgf 8和pax 2，正常表达，这表明Ran是不需要在眼睛发育的早期阶段。然而，早期视神经分化标志物p57 kip 2在中期（48 hpf）和晚期（72 hpf）不表达。我们还观察到视网膜神经元蛋白HuC和Neurolin的减少。神经元前基因ath 5，它首先决定了神经节细胞层发育的细胞命运，是检测不到的。此外，我们发现Ran与ADP-核糖基化因子样蛋白6相互作用蛋白1（Arl 6 ip 1）相关，该蛋白在视网膜发育中起作用，表明Ran与Arl 6 ip 1相关以调节视网膜发育。因此，虽然Ran的影响在早期指定的眼睛领域是最小的，Ran是需要在以后的发展阶段的视网膜细胞的增殖和分化。
Ras-related nuclear protein (Ran) is involved in cell division by regulating nucleocytoplasmic transport and modulating the assembly of tubulin. However, its function in embryonic development is unclear. We used zebrafish to study the roles of Ran in eye development. The ran transcripts were restrictedly expressed in head and eyes after the pharyngula stage. The microphthalmos, in which no ordered layers with differentiated retinal cells were detected, was observed in the ran-deficient embryos. They exhibited faster decline cyclinD1-expressed cells, suggesting that cell cycle regulation in retinae was defective. The apoptotic signals in the retinae of ran-deficient embryos remained low at early (24 hpf) stage. Early eye field specification markers, rx1 and pax6, were only slightly affected, and markers for establishing axon migration, fgf8 and pax2, were normally expressed, suggesting Ran is not required in the early stages of eye development. However, the early optic nerve differentiation marker p57kip2 was not expressed at middle (48 hpf) and late (72 hpf) stages. We also observed a decrease in the retinal neuron proteins HuC and Neurolin. The proneural gene ath5, which first determines the cell fate of the developing ganglion cell layer, was undetectable. Furthermore, we found that Ran was associated with ADP-ribosylation factor-like protein 6-interacting protein 1 (Arl6ip1), which plays a role in retinal development, suggesting that Ran associates with Arl6ip1 to regulate retinal development. Therefore, while the effects of Ran are minimal during early specification of the eye field, Ran is required for proliferation and differentiation of retinal cells at later developmental stages.