Zebrafish as an Emerging Model Organism to Study Angiogenesis in Development and Regeneration

Abstract

Angiogenesis is the process through which new blood vessels are formed from preexisting ones and plays a critical role in several conditions including embryonic development, tissue repair and disease. Moreover, enhanced therapeutic angiogenesis is a major goal in the field of regenerative medicine and efficient vascularization of artificial tissues and organs is one of the main hindrances in the implementation of tissue engineering approaches, while, on the other hand, inhibition of angiogenesis is a key therapeutic target to inhibit for instance tumor growth. During the last decades, the understanding of cellular and molecular mechanisms involved in this process has been matter of intense research. In this regard, several in vitro and in vivo models have been established to visualize and study migration of endothelial progenitor cells, formation of endothelial tubules and the generation of new vascular networks, while assessing the conditions and treatments that either promote or inhibit such processes. In this review, we address and compare the most commonly used experimental models to study angiogenesis in vitro and in vivo. In particular, we focus on the implementation of the zebrafish (Danio rerio) as a model to study angiogenesis and discuss the advantages and not yet explored possibilities of its use as model organism.

Identification and expression analysis of zebrafish testis-specific gene 10 (tsga10)

“…Due to the availability of zebrafish transgenic lines with endothelial expression of fluorescent proteins mediated by a vascular gene promoter, such as Tg(flk:EGFP) and Tg(fli1:EGFP), vascular and blood development can be visualized and analyzed in great detail. Finally, genetic studies have uncovered the preservation of molecular pathways between mammals and fish, making vasculogenesis research in zebrafish doubtlessly applicable for human health (Chavez et al, 2016).…”

A Reliable Preclinical Model to Study the Impact of Cigarette Smoke in Development and Disease

“…The zebrafish is a suitable model to study both developmental and regeneration processes. It has four main advantages relative to its murine counterpart: (1) external development, (2) small size and high fecundity, which support high-throughput studies, (3) optical clarity, and (4) availability of transgenic reporter lines that allow the visualization of specific cells and organs (Chávez, Aedo, Fierro, Allende, & Egaña, 2016). Additionally, adult zebrafish exhibit a remarkable regenerative potential in several tissues, including heart, fins, central nervous system, jaw, lateral line, hair cells, pancreas, liver, and kidneys (Liu et al, 2018).…”

In vivo imaging defines vascular interplay in the development of lymphocytic leukemia in zebrafish models

“…These features are also characteristic of zebrafish models of leukemia caused by forced expression of transgenic oncogenes like Myc in lymphocyte progenitor cells [3,16]. Angiogenesis in zebrafish is also similar to that of mammals, and has been well characterized by using VEGFR2 (Kdlr) and Fli1 transgenic reporter systems [17-19]. Tumor-related angiogenesis has also been demonstrated in zebrafish, in both early embryos and in xenograft systems in adult fish [20-22], although the latter models are profoundly immunosuppressed and may not provide an accurate representation of the tumor-vasculature crosstalk.…”