Introduction: in vivo cell biology in zebrafish.
Introduction: in vivo cell biology in zebrafish.
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简介：斑马鱼体内细胞生物学。
DOI：
10.1007/s00418-020-01931-4
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发表时间：
2020
影响因子：
2.3
通讯作者：
Scholpp S
中科院分区：
文献类型：
--
作者：
Scholpp S
细胞生物学研究生命的基本单位细胞的结构和功能。细胞结构、细胞通讯、细胞周期和细胞代谢是生物学这一分支的许多令人兴奋的主题。由组织化学和细胞生物学出版的“斑马鱼体内细胞生物学”特刊重点介绍了斑马鱼作为研究细胞许多功能的重要模式生物。在过去的几十年里，细胞生物学的重点是在体外培养细胞。体外细胞生物学的一个主要优点是可以测试细胞对药物的反应，以了解它们如何发挥作用以及生物体如何反应。使用细胞培养的最著名的进步之一可能是脊髓灰质炎疫苗的开发。在20世纪40年代和50年代初的高峰期，脊髓灰质炎每年在全世界造成50多万人瘫痪或死亡。缺乏大规模测试潜在疫苗的方法。使用第一个永生细胞系之一的HeLa细胞，在20世纪50年代成功地引入了疫苗。从那时起，研究人员使用这些传统的二维单层细胞培养物，因为它们相对便宜且易于获得，从而能够进行可靠且有效的高通量筛选细胞测定。然而，这些细胞培养系统的一个显著缺点是它们不能捕获器官系统复杂性内的细胞行为。这些简单的体外模型不能解释发育和组织稳态过程中不同细胞类型和细胞外基质之间的三维相互作用。这也可能反映在缓慢和昂贵的药物发现过程中。目前，许多药物在临床试验中失败，原因是对复杂环境中的细胞行为缺乏了解，导致缺乏疗效或因安全问题而失败。因此，最有希望提高我们对细胞生物学的理解从而提高药物开发的成功率的领域之一是获得更好地概括体内细胞生物学的模型生物。斑马鱼是研究完整脊椎动物体内细胞生物学许多方面的一个快速扩展和珍贵的模型系统。自20世纪80年代初作为现代实验模式生物引入以来，已经开发了许多用于成像和遗传操作的新工具。鉴于斑马鱼和其他脊椎动物之间的基因组高度相似，斑马鱼的许多关键发现也适用于人类。斑马鱼提供了多个显着的优势，组织培养模型，一方面和哺乳动物脊椎动物模型生物体，如小鼠和大鼠。斑马鱼胚胎的早期发育是外部的，快速的，视觉上可访问的。斑马鱼每周产几百个卵。这种高数量的后代对于脊椎动物的遗传作图研究和大规模筛选实验是有利的。斑马鱼可以在高密度的水族箱系统中饲养和维持，所需的空间和成本比哺乳动物所需的动物设施少得多。斑马鱼幼虫在受精后两天孵化，三天后开始积极进食。在这最初的五天里，所有主要的器官系统发育并开始运作。包括大规模基因组诱变、基因定位、转基因、蛋白质过表达、基因敲除、用于嵌合胚胎分析的细胞移植和化学筛选在内的技术进一步提高了这种模式生物的能力。斑马鱼胚胎和…
Cell biology studies the structure and function of cells—the basic unit of life. Cell architecture, cell communication, cell cycle, and cell metabolism are among many exciting topics of this branch of biology. This special issue “In vivo cell biology in zebrafish” presented by Histochemistry and Cell Biology focuses on the zebrafish as a vital model organism to study many functions of a cell. In the last decades, cell biology was focussing on culturing cells outside of a body. One major advantage of in vitro cell biology is the possibility to test the response of cells to drugs in order to understand how they function and how the organism would react. One of the most well-known advances using cell culture was probably the development of a vaccine against Polio. At its peak in the 1940s and early 1950s, Polio would paralyze or kill over half a million people worldwide every year. A way to test potential vaccines on a large scale was missing. Using one of the first immortal cell lines, the HeLa cells, a successful vaccine was introduced in the 1950s. Since then, researchers use these traditional two-dimensional monolayer cell cultures, because they are relatively cheap and simple to procure, enabling reliable and efficient cellular assays for high-throughput screening. However, a significant drawback of these cell culture systems is their failure to capture cellular behaviour within the complexity of an organ system. These simple in vitro models do not account for interactions between different cell types and extracellular matrix in a three-dimensional fashion during development and tissue homeostasis. This may also be reflected in slow and costly drug discovery processes. Currently, many drugs fail in clinical trials due to a lack of understanding of cell behaviour in a complex environment leading to a lack of efficacy or failure due to safety issues. Thus, one of the most promising areas expected to improve our understanding of cell biology—and thus the success rates in drug development—is the availability of model organisms that better recapitulate in vivo cell biology. The zebrafish, Danio rerio, is a fast expanding and precious model system for studying many aspects of cell biology within an intact vertebrate organism. Since its introduction as a modern experimental model organism in the early 1980s, many new tools have been developed for imaging and genetic manipulation. Given the high genomic similarities between zebrafish and other vertebrates, many of the critical discoveries in zebrafish are applicable to humans. Zebrafish provide multiple significant advantages over tissue culture models on one hand and mammalian vertebrate model organisms such as mice and rats on the other. Early development of zebrafish embryos is external, rapid, and visually accessible. Zebrafish produce several hundred eggs each week. This high number of offspring is advantageous for genetic mapping studies and large-scale screening experiments in vertebrates. Zebrafish can be raised and maintained in high-density aquarium systems requiring much less space and cost than the animal facilities necessary for mammals. Zebrafish larvae hatch two days after fertilization and begin actively feeding three days after. During these first five days, all major organ systems develop and begin functioning. Techniques including large-scale genome mutagenesis, gene mapping, transgenesis, protein overexpression, gene knockout, cell transplantation for chimeric embryo analysis, and chemical screens have further increased the power of this model organism.However, the main advantage of this model system is the accessibility of the organism during embryogenesis. Zebrafish embryos and …