Closing the Gap: Mechanisms of Epithelial Fusion During Optic Fissure Closure.

Closing the Gap: Mechanisms of Epithelial Fusion During Optic Fissure Closure.
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DOI:
10.3389/fcell.2020.620774
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发表时间:
2020
影响因子:
5.5
通讯作者:
Rainger J
Rainger J
中科院分区:
生物学2区
文献类型:
--
作者:
Chan BHC;Moosajee M;Rainger J

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眼发育早期发生的一个关键胚胎过程是视神经裂隙闭合(OFC)。这个融合过程关闭了腹侧视裂,完成了三维眼的周向连续性。它的定义是沿整个腹侧视杯近端和远端轴方向相反的神经上皮聚集融合,包括未来的神经视网膜、视网膜色素上皮(RPE)、视神经、睫状体和虹膜。一旦这些发生,融合缝内的细胞分化为功能视觉系统的组成部分。OFC的正确发育和进展,以及沿该轴融合缘的持续完整性,对眼睛的整体结构非常重要。OFC的失败导致眼结肠瘤,这是儿童视力障碍的重要原因,可能与几种复杂的眼部表型相关,包括小眼症和前段发育不良。尽管已经发现了大量基因,但最终介导融合的确切途径尚未发现,这反映了该过程的生物复杂性和遗传异质性。本综述将重点介绍最近的发育研究如何特别关注OFC的上皮融合方面,应用一系列模式生物(包括鱼类、鸟类和哺乳动物物种),利用新兴的高分辨率实时成像技术,转基因荧光模型,以及对节段性解剖裂隙组织的无偏倚转录组学分析。讨论融合过程的关键方面,包括基底膜动力学,独特的细胞行为,以及介导融合的细胞的身份和命运。这些将在已知的背景下进行,以及这些如何指向新的研究途径。
A key embryonic process that occurs early in ocular development is optic fissure closure (OFC). This fusion process closes the ventral optic fissure and completes the circumferential continuity of the 3-dimensional eye. It is defined by the coming together and fusion of opposing neuroepithelia along the entire proximal-distal axis of the ventral optic cup, involving future neural retina, retinal pigment epithelium (RPE), optic nerve, ciliary body, and iris. Once these have occurred, cells within the fused seam differentiate into components of the functioning visual system. Correct development and progression of OFC, and the continued integrity of the fused margin along this axis, are important for the overall structure of the eye. Failure of OFC results in ocular coloboma—a significant cause of childhood visual impairment that can be associated with several complex ocular phenotypes including microphthalmia and anterior segment dysgenesis. Despite a large number of genes identified, the exact pathways that definitively mediate fusion have not yet been found, reflecting both the biological complexity and genetic heterogeneity of the process. This review will highlight how recent developmental studies have become focused specifically on the epithelial fusion aspects of OFC, applying a range of model organisms (spanning fish, avian, and mammalian species) and utilizing emerging high-resolution live-imaging technologies, transgenic fluorescent models, and unbiased transcriptomic analyses of segmentally-dissected fissure tissue. Key aspects of the fusion process are discussed, including basement membrane dynamics, unique cell behaviors, and the identities and fates of the cells that mediate fusion. These will be set in the context of what is now known, and how these point the way to new avenues of research.
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