Abstract
For nearly a decade, researchers in the field of pediatric oncology have been using zebrafish as a model for understanding the contributions of genetic alternations to the pathogenesis of neuroblastoma (NB), and exploring the molecular and cellular mechanisms that underlie neuroblastoma initiation and metastasis. In this review, we will enumerate and illustrate the key advantages of using the zebrafish model in NB research, which allows researchers to: monitor tumor development in real-time; robustly manipulate gene expression (either transiently or stably); rapidly evaluate the cooperative interactions of multiple genetic alterations to disease pathogenesis; and provide a highly efficient and low-cost methodology to screen for effective pharmaceutical interventions (both alone and in combination with one another). This review will then list some of the common challenges of using the zebrafish model and provide strategies for overcoming these difficulties. We have also included visual diagram and figures to illustrate the workflow of cancer model development in zebrafish and provide a summary comparison of commonly used animal models in cancer research, as well as key findings of cooperative contributions between MYCN and diverse singling pathways in NB pathogenesis.
Highlights
Over the past ten years, zebrafish have become an increasingly popular tool for scientists conducting biomedical studies and other research
2003, the first zebrafish genetic cancer model was reported by Drs David Langenau and Thomas Look, in which the MYC oncogene was overexpressed under control of the rag2 promoter, resulting in the development of T cell leukemia in the transgenic animal [2]
Zebrafish are relatively simple to use when compared to rodent models that require multiple time-consuming steps including a period of superovulation by pregnant mare serum (PMS) in the early afternoon followed by human chorionic gonadotropin treatment [72], labor-intensive oocyte harvesting, in vitro fertilization, and embryo implantation
Summary
Over the past ten years, zebrafish have become an increasingly popular tool for scientists conducting biomedical studies and other research. In. 2003, the first zebrafish genetic cancer model was reported by Drs David Langenau and Thomas Look, in which the MYC oncogene was overexpressed under control of the rag promoter, resulting in the development of T cell leukemia in the transgenic animal [2]. MYCN and mutationally activated ALK (the most commonly mutated genes in primary neuroblastoma [34,35,36,37] and an attractive candidate for targeted therapy [38,39]), were expressed under control of the dopamine-beta-hydroxylase (dβh) promoter [33] Following this initial effort on modeling NB in zebrafish, many new transgenic fish lines were developed, uncovering additional novel genetic alterations that cooperate with MYCN or c-MYC during NB pathogenesis.
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