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研究斑马鱼视网膜神经发生的方法。

Approaches to study neurogenesis in the zebrafish retina.

作者信息

Avanesov Andrei, Malicki Jarema

机构信息

Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.

出版信息

Methods Cell Biol. 2004;76:333-84. doi: 10.1016/s0091-679x(04)76016-1.

Abstract

Similar to other vertebrate species, the zebrafish retina is simpler than other regions of the central nervous system (CNS). Relative simplicity, rapid development, and accessibility to genetic analysis make the zebrafish retina an excellent model system for the studies of neurogenesis in the vertebrate CNS. Numerous genetic screens have led to isolation of an impressive collection of mutations affecting the retina and the retinotectal projection in zebrafish. Mutant phenotypes are being studied using a rich variety of markers: antibodies, RNA probes, retrograde and anterograde tracers, as well as transgenic lines. Particularly impressive progress has been made in the characterization of the zebrafish genome. Consequently, positional and candidate cloning of mutant genes are now fairly easy to accomplish in zebrafish. Many mutant genes have, in fact, already been cloned and their analysis has provided important insights into the gene circuitry that regulates retinal neurogenesis. Genetic screens for visual system defects will continue in the future and progressively more sophisticated screening approaches will make it possible to detect a variety of subtle mutant phenotypes in retinal development. The remarkable evolutionary conservation of the vertebrate eye provides the basis for the use of the zebrafish retina as a model of human disorders. Some of the genetic defects of the zebrafish retina indeed resemble human retinopathies. As new techniques are being introduced and improved at a rapid pace, the zebrafish will continue to be an important organism for the studies of the vertebrate visual system.

摘要

与其他脊椎动物物种相似,斑马鱼的视网膜比中枢神经系统(CNS)的其他区域更简单。相对简单、发育迅速以及便于进行遗传分析,使得斑马鱼视网膜成为研究脊椎动物中枢神经系统神经发生的极佳模型系统。众多的遗传筛选已导致分离出一系列令人印象深刻的影响斑马鱼视网膜和视网膜顶盖投射的突变。正在使用丰富多样的标记物研究突变体表型:抗体、RNA探针、逆行和顺行示踪剂,以及转基因品系。在斑马鱼基因组的表征方面取得了特别显著的进展。因此,在斑马鱼中突变基因的定位克隆和候选克隆现在相当容易完成。事实上,许多突变基因已经被克隆,对它们的分析为调节视网膜神经发生的基因回路提供了重要见解。未来将继续进行视觉系统缺陷的遗传筛选,并且越来越复杂的筛选方法将使得检测视网膜发育中各种细微的突变体表型成为可能。脊椎动物眼睛显著的进化保守性为将斑马鱼视网膜用作人类疾病模型提供了基础。斑马鱼视网膜的一些遗传缺陷确实类似于人类视网膜病变。随着新技术的迅速引入和改进,斑马鱼将继续成为研究脊椎动物视觉系统的重要生物体。

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