“…Furthermore, microscopic studies are eased by the transparency of the embryo and its small size, avoiding body hindrance under the microscope. The model has been widely used in developmental and cell biology, as well as in cancer biology [ 10 , 11 ], and recently emerged as a powerful system to track viral dissemination in vivo [ 12 , 13 ]. Zebrafish in the Context of the SARS-Co-2 Pandemic Numerous labs are rushing toward the development of a zebrafish model to study SARS-CoV-2, but no reports have been formally published to date, suggesting that the virus causing COVID-19 may not vigorously infect zebrafish.…”
Section: Tracking Viral Dissemination From the Bloodstream Using Zebrmentioning
Dissemination and replication of viruses into hosts is a multistep process where viral particles infect, navigate, and indoctrinate various cell types. Viruses can reach tissues that are distant from their infection site by subverting subcellular mechanisms in ways that are, sometimes, disruptive. Modeling these steps, at appropriate resolution and within animal models, is cumbersome. Yet, mimicking these strategies
in vitro
fails to recapitulate the complexity of the cellular ecosystem. Here, we will discuss relevant
in vivo
platforms to dissect the cellular and molecular programs governing viral dissemination and briefly discuss organoid and
ex vivo
alternatives. We will focus on the zebrafish model and will describe how it provides a transparent window to unravel new cellular mechanisms of viral dissemination
in vivo
.
“…Furthermore, microscopic studies are eased by the transparency of the embryo and its small size, avoiding body hindrance under the microscope. The model has been widely used in developmental and cell biology, as well as in cancer biology [ 10 , 11 ], and recently emerged as a powerful system to track viral dissemination in vivo [ 12 , 13 ]. Zebrafish in the Context of the SARS-Co-2 Pandemic Numerous labs are rushing toward the development of a zebrafish model to study SARS-CoV-2, but no reports have been formally published to date, suggesting that the virus causing COVID-19 may not vigorously infect zebrafish.…”
Section: Tracking Viral Dissemination From the Bloodstream Using Zebrmentioning
Dissemination and replication of viruses into hosts is a multistep process where viral particles infect, navigate, and indoctrinate various cell types. Viruses can reach tissues that are distant from their infection site by subverting subcellular mechanisms in ways that are, sometimes, disruptive. Modeling these steps, at appropriate resolution and within animal models, is cumbersome. Yet, mimicking these strategies
in vitro
fails to recapitulate the complexity of the cellular ecosystem. Here, we will discuss relevant
in vivo
platforms to dissect the cellular and molecular programs governing viral dissemination and briefly discuss organoid and
ex vivo
alternatives. We will focus on the zebrafish model and will describe how it provides a transparent window to unravel new cellular mechanisms of viral dissemination
in vivo
.
“…Since we found that the lack of Lphn2a results in the abnormal organization of TJs between ECs in vivo ( Fig. 4C), we sought to investigate the impact of LPHN2 on the extravasation of cancer cells that can be effectively tracked and quantified by using the zebrafish embryo (Follain et al, 2018;Osmani & Goetz, 2019). To this aim, fluorescently-labeled mouse (B16F10) or human (SK-MEL-28) melanoma cells were injected in the duct of Cuvier of Tg(kdrl:EGFP) s843 wild type or lphn2a -/zebrafish embryos and their metastatic extravasation potential was quantified by measuring the number of tumor cells outside the vessels in the caudal plexus where the circulating tumor cells (CTCs) preferentially arrested and extravasated (Follain et al, 2018;Hyenne et al, 2019).…”
Dynamic modulation of endothelial cell (EC) adhesion to extracellular matrix (ECM) in response to mechanostimuli is essential for blood vessel patterning and functioning. Yet, the molecular mechanisms involved in this biological process are far to be completely deciphered. Here, we identify the adhesion G protein-coupled receptor (ADGR) Latrophilin 2 (LPHN2) as a novel determinant of vascular morphogenesis and endothelial barrier function. In cultured ECs, endogenous LPHN2 localizes at ECM adhesions, signals through cAMP/Rap1, and, via its fibronectin-leucine-rich transmembrane (FLRT)-binding domain, negatively regulates ECM-elicited haptotaxis. ECs also express endogenous FLRT2 ligand that promotes cAMP/Rap1 signaling and hinders haptotaxis in a LPHN2-dependent manner. Vascular ECs of lphn2a knock-out zebrafish embryos become abnormally stretched, display a hyperactive Hippo mechanosensing pathway, and lack proper intercellular junctions. Indeed, intravascularly injected cancer cells extravasate more easily in lphn2a null animals. Thus, LPHN2 ligands, such as FLRT2, may be therapeutically exploited to interfere with cancer metastatic dissemination.
“…Indeed, tumor xenografts in zebrafish embryos represent an advantageous platform to perform drug screening of new anticancer molecules. Because of the permeability of zebrafish embryos to small molecules, these drugs can be added directly to the embryo water, whereas larger or not water-soluble molecules can be injected into the blood circulation (Konantz et al 2012, Fior et al 2017, Hason & Bartunek 2019, Osmani & Goetz 2019.…”
Section: Zebrafish Model In Cancer Researchmentioning
confidence: 99%
“…Although rodents represent the main animal model in cancer research, the use of this model in the field of NETs is very limited. In the last decade, the use of zebrafish (Danio rerio) in biomedical research is growing exponentially, with relevant applications in studying human diseases (Lohr & Hammerschmidt 2011), such as cancer modeling (Astell & Sieger 2019, Hason & Bartunek 2019, Osmani & Goetz 2019. In 2014, we have published an article providing a comprehensive overview of zebrafish in NET research, describing genetic models and our preliminary results of NET xenotransplantation in zebrafish embryos.…”
Neuroendocrine tumors (NETs) are a class of rare and heterogeneous neoplasms that originate from the neuroendocrine system. In several cases, these neoplasms can release bioactive hormones leading to characteristic clinical syndromes and hormonal dysregulations with detrimental impact on the quality of life and survival of these patients. Only few animal models are currently available to investigate pathogenesis, progression and functional syndromes in NETs and to identify new therapeutic strategies. The tropical teleost zebrafish (Danio rerio) is a popular vertebrate model system that offers unique advantages for the study of several biological processes, ranging from embryonic development to human diseases such as cancer. In this review, we summarize recent advances on zebrafish models for NET preclinical research that take advantage of modern genetic and transplantable technologies. In the future, these tools may have a role in the treatment decision-making and tertiary prevention of NETs.
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