Toolbox in a tadpole: Xenopus for kidney research

Abstract

Xenopus is a versatile model organism increasingly used to study organogenesis and genetic diseases. The rapid embryonic development, targeted injections, loss- and gain-of-function experiments and an increasing supply of tools for functional in vivo analysis are unique advantages of the Xenopus system. Here, we review the vast array of methods available that have facilitated its transition into a translational model. We will focus primarily on how these methods have been employed in the study of kidney development, renal function and kidney disease. Future advances in the fields of genome editing, imaging and quantitative 'omics approaches are likely to enable exciting and novel applications for Xenopus to deepen our understanding of core principles of renal development and molecular mechanisms of human kidney disease. Thus, using Xenopus in clinically relevant research diversifies the narrowing pool of "standard" model organisms and provides unique opportunities for translational research.

<b><i>Xenopus</i></b>: An Undervalued Model Organism to Study and Model Human Genetic Disease

“…Kidney disease is another very promising area in which Xenopus offers great potential, because the tadpole differentiates one fully functional nephron on either side, ideally suited to studying the various steps of kidney development from tubulogenesis to segmentation and active filtration, again in a one-sided manner with its internal control [Lienkamp et al, 2012;Hoff et al, 2013;Lienkamp, 2016]. Both these examples have recently been covered by excellent reviews, to which the interested reader is referred [Garfinkel and Khokha, 2017;Getwan and Lienkamp, 2017]. A large group of diverse genetic diseases that is particularly well qualified to be studied in Xenopus is represented by the so-called ciliopathies [Fliegauf et al, 2007;Mitchison and Valente, 2017].…”

“…A number of transgenic lines are already available from the US and European resource centers (Xenbase.org; xenopusresource.org), and new ones can be generated fairly quickly [Aslan et al, 2017;Moreno-Mateos et al, 2017]. Candidate genes and alleles for human genetic disease are being identified at an enormous pace: analyses such as genome-wide association studies, GWAS, whole-exome sequencing, WES, and DNA and RNA sequencing from healthy and diseased tissues generate long lists of candidate genes and alleles that overwhelm biomedical researchers with the task of evaluating large data sets rapidly and at a manageable cost [MacArthur et al, 2014;Samocha et al, 2014;Getwan and Lienkamp, 2017]. The demand is for models to verify or discard candidate genes and to establish predictive models in which therapeutic options can be developed and tested.…”

“…The possibility to directly observe embryonic development and even perform live cell imaging has been extensively used with great success in zebrafish. However, this is not a unique feature of zebrafish; kidney development and neural crest cell migration, for example, have been directly imaged in live frog em- bryos at great temporal and spatial resolution [Lienkamp et al, 2010[Lienkamp et al, , 2012Szabó et al, 2016;Getwan and Lienkamp, 2017]. Zebrafish also have certain organ-specific limitations.…”

Characterization of Xenopus laevis guanine deaminase reveals new insights for its expression and function in the embryonic kidney

“…Still, we wondered whether Gda might be important for kidney function. It has been demonstrated that an altered osmoregulatory function of the kidney leads to edema formation due to water retention (Wessely and Tran, 2011;Krneta-Stankic et al, 2017) and evaluation of edema has been widely used to assess kidney function (Getwan and Lienkamp, 2017;Krneta-Stankic et al, 2017). Thus, we used an antisense oligonucleotide to knock down (KD) gda by 50% (Fig.…”

An in vivo brain–bacteria interface: the developing brain as a key regulator of innate immunity

“…We developed a Xenopus model in which we could study braindependent events in embryogenesis: the brain is removed during early embryonic stages, but the animal can be kept alive and development continues. The ability of this vertebrate, a popular model for numerous biomedical contexts, [27][28][29][30][31][32][33][34] to survive and develop without a brain provides a unique opportunity to understand the role of the brain in diverse systems-level outcomes. Our prior research into brain-dependent developmental signaling revealed that the nascent brain, even before being fully formed, plays an instructive role in patterning somitic muscle and peripheral neural networks.…”