Advances in the use of Xenopus for successful drug screening

ABSTRACT

Introduction: Understanding embryogenesis currently relies largely on the control of gene expression via several signaling pathways. Many of the embryonic signaling pathways guiding embryological events are implicated in diseases that lack effective cure or treatment. Because of the large number and size of the eggs, the rapid development of the embryos and the fact they are amenable to pharmacological, surgical and genetic techniques, Xenopus laevis has been successfully used in searching for compounds that target embryonic signaling pathways.

Areas covered: Here, the authors address the use of amphibian eggs/embryos in successful chemical screenings; egg extracts as well as embryo phenotypes have been assayed to reveal drug toxicology effects and novel compounds acting in the Wnt/β-catenin signaling pathway. They do not discuss the use of Xenopus oocyte two-electrode voltage clamps or genome editing tools as approaches for drug discovery because they have been discussed elsewhere.

Expert opinion: While high-throughput screening is commonly performed in egg extracts, the embryo axes perturbation system is more suited to the refinement and/or the validation of drug discovery targeting embryonic signaling (particularly the Wnt/β-catenin pathway). In addition, Xenopus has also been used in FETAX (frog embryo teratogenesis assay: Xenopus) to address chemical toxic/teratogenic effects. However, further studies are necessary.

KEYWORDS:

• Amphibian embryo
• embryonic axis formation
• Wnt
• translational developmental biology
• chemical screening
• FETAX
• natural compounds
• flavonoids

Article highlights

• Xenopus oocyte/embryo is a bright spot within the field of drug discovery;

• Amphibians share some important apomorphies with mammals, such as development of limbs, lungs, a complex heart and immune system;

• Xenopus oocyte/embryo is a robust system for drug bath, microinjection, microsurgery and tissue transplant experiments;

• FETAX is a classical protocol to identify drugs that pose potential teratogenic hazards.

• The Xenopus egg extract system allows the analysis of a large number of compounds and therefore is an alternative to the in vitro assays;

• Wnt/β-catenin pathway perturbation provides straightforward and reproducible phenotypes;

• A flow chart is presented as basis to design functional chemical screenings aiming to find new modulators of Wnt/β-catenin signaling pathway in Xenopus embryo.

This box summarizes key points contained in the article.

Acknowledgments

The authors gratefully acknowledge S Rodrigues for their frog technical support.

Declaration of interest

Lorena Agostini Maia is working on her PhD via the Graduate Program in Morphological Sciences at the Federal University of Rio de Janeiro and is supported by a CNPq fellowship while Ian Randolph Velloso is a master’s student of the Graduate Program in Morphological Sciences at the Federal University of Rio de Janeiro and is supported by a CAPES fellowship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico [Grant No. 462073/2014-9] from the Ministério da Ciência, Tecnologia e Inovação, CNPQ, Fundação CAPES and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro [FAPERJ Grant No. #E-26/202.964/2015].