Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future.
Zebrafish Models of Neurodevelopmental Disorders: Past, Present, and Future.
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DOI：
10.3389/fnmol.2018.00294
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发表时间：
2018
影响因子：
4.8
通讯作者：
Hoffman EJ
中科院分区：
文献类型：
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作者：
Sakai C;Ijaz S;Hoffman EJ
斑马鱼越来越多地被用作模型系统来研究与神经发育障碍相关的风险基因的功能。这在很大程度上是由于斑马鱼的独特特征，使其成为用于此目的的最佳系统，包括透明胚胎的快速外部发育，这使得能够在早期阶段直接观察发育中的神经系统，大型后代，这为进行高通量药理学筛选以鉴定简单行为表型的小分子抑制剂提供了相当大的易处理性，和基因操作的简易性，CRISPR/Cas9基因编辑技术的出现极大地促进了这一点。这篇综述文章的重点是利用斑马鱼系统的这些优势进行基因功能分析的研究，这些基因与以下神经发育障碍密切相关：自闭症谱系障碍（ASD），癫痫，智力残疾（ID）和精神分裂症。我们主要集中在研究描述早期形态和行为表型在胚胎和幼虫阶段造成的风险基因功能丧失。我们强调从这些研究中获得的风险基因功能的基本机制的见解，以及迄今为止的研究的局限性。最后，我们讨论了斑马鱼体内神经回路成像的进展，这有望通过阐明与神经发育障碍相关的新回路水平机制来改变使用斑马鱼模型的研究。
Zebrafish are increasingly being utilized as a model system to investigate the function of the growing list of risk genes associated with neurodevelopmental disorders. This is due in large part to the unique features of zebrafish that make them an optimal system for this purpose, including rapid, external development of transparent embryos, which enable the direct visualization of the developing nervous system during early stages, large progenies, which provide considerable tractability for performing high-throughput pharmacological screens to identify small molecule suppressors of simple behavioral phenotypes, and ease of genetic manipulation, which has been greatly facilitated by the advent of CRISPR/Cas9 gene editing technologies. This review article focuses on studies that have harnessed these advantages of the zebrafish system for the functional analysis of genes that are strongly associated with the following neurodevelopmental disorders: autism spectrum disorders (ASD), epilepsy, intellectual disability (ID) and schizophrenia. We focus primarily on studies describing early morphological and behavioral phenotypes during embryonic and larval stages resulting from loss of risk gene function. We highlight insights into basic mechanisms of risk gene function gained from these studies as well as limitations of studies to date. Finally, we discuss advances in in vivo neural circuit imaging in zebrafish, which promise to transform research using the zebrafish model by illuminating novel circuit-level mechanisms with relevance to neurodevelopmental disorders.
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影响因子：
3.5
作者：
Eachus H;Bright C;Cunliffe VT;Placzek M;Wood JD;Watt PJ
通讯作者：
Watt PJ
影响因子：
7
作者：
Auer TO;Duroure K;De Cian A;Concordet JP;Del Bene F
通讯作者：
Del Bene F
影响因子：
1.5
作者：
Draper, BW;Morcos, PA;Kimmel, CB
通讯作者：
Kimmel, CB
影响因子：
4.5
作者：
Anderson JL;Mulligan TS;Shen MC;Wang H;Scahill CM;Tan FJ;Du SJ;Busch-Nentwich EM;Farber SA
通讯作者：
Farber SA
影响因子：
64.8
作者：
通讯作者：
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