The disarrayed mutation results in cell cycle and neurogenesis defects during retinal development in zebrafish

The disarrayed mutation results in cell cycle and neurogenesis defects during retinal development in zebrafish
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DOI:
10.1186/1471-213x-7-28
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发表时间:
2007-04-05
影响因子:
--
通讯作者:
Link, Brian A.
Link, Brian A.
中科院分区:
生物学4区
文献类型:
--
作者:
Baye, Lisa M.;Link, Brian A.

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背景:脊椎动物的视网膜源自视杯的增殖性神经上皮细胞。在视网膜发育过程中,细胞增殖以及细胞周期退出和神经发生的过程在神经上皮祖细胞中协调。先前的研究已经证明细胞周期和神经发生之间的相互影响。然而,脊椎动物视网膜中细胞周期调节和神经发生的具体机制和确切关系仍然很大程度上未知。 结果:我们分离并表征了斑马鱼突变体,disarrayed (dry(a64)),其在细胞周期调节和神经发生方面表现出视网膜缺陷。 By 42 hours post fertilization, disarrayed mutants show small eyes and a reduced forebrain.发育的其他方面似乎正常。 Although retinogenesis is delayed, mutant retinal cells eventually differentiate to all major cell types.使用 BrdU 和直接成像技术检查混乱的有丝分裂周期表明,视网膜神经上皮细胞的细胞周期周期延长,细胞周期退出和神经发生率降低,尽管神经发生在适当的发育时间启动。遗传镶嵌分析表明,disarrayed 的细胞周期表型是细胞非自主的。结论:disarrayed 突变体在细胞周期调节和神经发生方面均显示缺陷,并为视网膜发育过程中这些过程的协调调节提供了见解。
Background: The vertebrate retina is derived from proliferative neuroepithelial cells of the optic cup. During retinal development, cell proliferation and the processes of cell cycle exit and neurogenesis are coordinated in neuroepithelial progenitor cells. Previous studies have demonstrated reciprocal influences between the cell cycle and neurogenesis. However the specific mechanisms and exact relationships of cell cycle regulation and neurogenesis in the vertebrate retina remain largely unknown.Results: We have isolated and characterized a zebrafish mutant, disarrayed (dry(a64)), which exhibits retinal defects in cell cycle regulation and neurogenesis. By 42 hours post fertilization, disarrayed mutants show small eyes and a reduced forebrain. Other aspects of development appear normal. Although retinogenesis is delayed, mutant retinal cells eventually differentiate to all major cell types. Examination of the disarrayed mitotic cycle using BrdU and direct imaging techniques revealed that retinal neuroepithelial cells have an extended cell cycle period and reduced rate of cell cycle exit and neurogenesis, despite the fact that neurogenesis initiates at the appropriate time of development. Genetic mosaic analyses indicate that the cell cycle phenotype of disarrayed is cell-non-autonomous.Conclusion: The disarrayed mutant shows defects in both cell cycle regulation and neurogenesis and provides insights into the coordinated regulation of these processes during retinal development.