Xenopus leads the way: Frogs as a pioneering model to understand the human brain.
Xenopus leads the way: Frogs as a pioneering model to understand the human brain.
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非洲爪蟾带路：青蛙作为了解人类大脑的先驱模型。
DOI：
10.1002/dvg.23405
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Willsey HR
中科院分区：
文献类型：
--
作者：
Exner CRT;Willsey HR
从胚胎学领域的悠久历史到遗传学的最新进展，非洲爪龙一直是理解人类大脑不可或缺的模型。基础研究使我们第一次了解主要的胚胎模式事件，为研究器官发生和器官功能的新途径提供了重要的背景。非洲爪蟾（Xenopus laevis）和热带爪蟾（tropicalis）中可用的大量工具允许对从分子到行为的各个层面的发育现象进行调查，CRISPR技术的应用使人类疾病风险基因的研究能够以更高的通量方式进行。作为唯一一种主要的四足动物模型，青蛙的所有发育阶段都很容易被操纵和观察，这为研究最早阶段的器官发育提供了独特的机会。所有这些特征使非洲爪蟾成为研究大脑发育的首要模型，这是一个众所周知的复杂过程，需要了解从受精到器官发生等所有阶段。重要的是，大脑发育的核心过程在爪蟾和人类之间是保守的，强调了该模型的优势。这篇综述首先总结了在两栖动物身上的发现，这些发现构成了脊椎动物神经发育生物学的基石，然后讨论了最近的进展，这些进展使我们对爪蟾的大脑发育以及与人类发育和疾病的关系有了更深入的了解。随着我们进入一个以患者为导向的基因发现的新时代，Xenopus提供了非凡的潜力，可以揭示人类大脑疾病背后的保守生物学，并朝着合理的药物设计迈进。
From its long history in the field of embryology to its recent advances in genetics, Xenopus has been an indispensable model for understanding the human brain. Foundational studies that gave us our first insights into major embryonic patterning events serve as a crucial backdrop for newer avenues of investigation into organogenesis and organ function. The vast array of tools available in Xenopus laevis and tropicalis allows interrogation of developmental phenomena at all levels, from the molecular to the behavioral, and the application of CRISPR technology has enabled the investigation of human disorder risk genes in a higher-throughput manner. As the only major tetrapod model in which all developmental stages are easily manipulated and observed, frogs provide the unique opportunity to study organ development from the earliest stages. All of these features make Xenopus a premier model for studying the development of the brain, a notoriously complex process that demands an understanding of all stages from fertilization to organogenesis and beyond. Importantly, core processes of brain development are conserved between Xenopus and human, underlining the advantages of this model. This review begins by summarizing discoveries made in amphibians that form the cornerstones of vertebrate neurodevelopmental biology and goes on to discuss recent advances that have catapulted our understanding of brain development in Xenopus and in relation to human development and disease. As we engage in a new era of patient-driven gene discovery, Xenopus offers exceptional potential to uncover conserved biology underlying human brain disorders and move towards rational drug design.
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