Zebrafish as a Model for Fetal Alcohol Spectrum Disorders.
Zebrafish as a Model for Fetal Alcohol Spectrum Disorders.
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DOI：
10.3389/fphar.2021.721924
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发表时间：
2021
影响因子：
5.6
通讯作者：
Kudoh T
中科院分区：
文献类型：
--
作者：
Alsakran A;Kudoh T
在这篇综述中，我们将讨论斑马鱼作为研究人类胎儿酒精谱系障碍（FASD）机制的模型。我们将概述迄今为止对FASD的研究，并将重点讨论酒精在早期胚胎发生过程中改变细胞迁移的机制，包括囊胚，原肠胚和器官发生阶段，随后导致脑和其他组织的形态缺陷。FASD是由孕妇体内酒精含量升高引起的。FASD的症状包括小头畸形、前脑无裂畸形、颅面畸形和严重情况下伴有出生缺陷的心脏缺陷，在较轻的情况下，症状导致发育和学习障碍。透明的斑马鱼胚胎提供了一个理想的模型系统来研究遗传，细胞和有机体对酒精的反应。在斑马鱼胚胎发育过程中，从囊胚/原肠胚阶段的干细胞基因表达、原肠胚细胞运动、中枢神经系统的形态发生和神经元发育等多个方面观察到酒精的影响。这些数据表明，乙醇抑制收敛，延伸，和epiboly细胞运动在原肠胚阶段，并导致正常的神经板形成失败。随后，其他细胞运动，包括神经形成，眼野形态发生和神经嵴迁移也受到抑制，导致大脑和脊髓畸形，包括小头畸形，独眼畸形，脊柱裂和颅面畸形。在斑马鱼中测试细胞迁移将为酒精和其他相关化学物质的毒性提供方便的生物标志物，并研究大脑发育后目标信号通路之间的分子联系。
In this review, we will discuss zebrafish as a model for studying mechanisms of human fetal alcohol spectrum disorders (FASDs). We will overview the studies on FASDs so far and will discuss with specific focus on the mechanisms by which alcohol alters cell migration during the early embryogenesis including blastula, gastrula, and organogenesis stages which later cause morphological defects in the brain and other tissues. FASDs are caused by an elevated alcohol level in the pregnant mother’s body. The symptoms of FASDs include microcephaly, holoprosencephaly, craniofacial abnormalities, and cardiac defects with birth defect in severe cases, and in milder cases, the symptoms lead to developmental and learning disabilities. The transparent zebrafish embryo offers an ideal model system to investigate the genetic, cellular, and organismal responses to alcohol. In the zebrafish, the effects of alcohol were observed in many places during the embryo development from the stem cell gene expression at the blastula/gastrula stage, gastrulation cell movement, morphogenesis of the central nervous system, and neuronal development. The data revealed that ethanol suppresses convergence, extension, and epiboly cell movement at the gastrula stage and cause the failure of normal neural plate formation. Subsequently, other cell movements including neurulation, eye field morphogenesis, and neural crest migration are also suppressed, leading to the malformation of the brain and spinal cord, including microcephaly, cyclopia, spinal bifida, and craniofacial abnormalities. The testing cell migration in zebrafish would provide convenient biomarkers for the toxicity of alcohol and other related chemicals, and investigate the molecular link between the target signaling pathways, following brain development.
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通讯作者：
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