Exner CRT and Willsey HR (2021), Xenopus leads the way: Frogs as a pioneering mo...

XB-ART-57663

Genesis 2021 Feb 01;591-2:e23405. doi: 10.1002/dvg.23405.

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Xenopus leads the way: Frogs as a pioneering model to understand the human brain.

Exner CRT , Willsey HR .

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From its long history in the field of embryology to its recent advances in genetics, Xenopus has been an indispensable model for understanding the human brain. Foundational studies that gave us our first insights into major embryonic patterning events serve as a crucial backdrop for newer avenues of investigation into organogenesis and organ function. The vast array of tools available in Xenopus laevis and Xenopus tropicalis allows interrogation of developmental phenomena at all levels, from the molecular to the behavioral, and the application of CRISPR technology has enabled the investigation of human disorder risk genes in a higher-throughput manner. As the only major tetrapod model in which all developmental stages are easily manipulated and observed, frogs provide the unique opportunity to study organ development from the earliest stages. All of these features make Xenopus a premier model for studying the development of the brain, a notoriously complex process that demands an understanding of all stages from fertilization to organogenesis and beyond. Importantly, core processes of brain development are conserved between Xenopus and human, underlining the advantages of this model. This review begins by summarizing discoveries made in amphibians that form the cornerstones of vertebrate neurodevelopmental biology and goes on to discuss recent advances that have catapulted our understanding of brain development in Xenopus and in relation to human development and disease. As we engage in a new era of patient-driven gene discovery, Xenopus offers exceptional potential to uncover conserved biology underlying human brain disorders and move towards rational drug design.

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Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: dlx2 dlx5 egr2 emx1 emx2 en1 en2 eomes fgf8 foxa2 foxg1 gbx2.1 gsx1 gsx2 hoxb9 isl1 lhx1 nkx2-1 otx2 pax6 shh tbr1 tcf4 wnt1

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???displayArticle.omims??? GILLES DE LA TOURETTE SYNDROME; GTS [+]

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	FIGURE 1 Summary of key techniques used in Xenopus to study brain development. Several important techniques core to the Xenopus neurodevelopmental biology toolkit are diagrammed here, although the authors note that this figure is not meant to be an exhaustive summary of available technologies, and that these methods are also applicable to the study of other developmental processes. Top panel (a): Summary of advantages of the Xenopus systems and brief overview of central nervous system development. Light blue indicates neural tissues at the embryonic and larval stages shown. Orientations: lateral view with animal pole to the top (oocyte, embryo), lateral view with dorsal to the right (gastrula), dorsal view with anterior to the top (neurula and tadpole), lateral view with anterior to the left (tailbud). Middle panels (b–d): common techniques used to manipulate Xenopus development, including targeted injection with any of several reagents (b), treatment with pharmacological agents (c), and two examples of explant techniques (d). Note that these methods can be used separately or in combination, as appropriate for the scientific questions of interest. Bottom panels (e–i): common methods for characterizing typical development or assessing the consequences of experimental manipulations (see b–d) on development. Diagrams depict hypothetical example results based on data from several references; see text for citations. In (e), from left to right: mRNA in situ hybridization shows a reduction in krox20 and hoxb9 expression, a posterior shift in krox20 expression, and no change in otx2 expression on the injected side of a unilaterally manipulated embryo; staining with an antibody against a pan‐neural protein shows reduced brain size on the injected side of a unilaterally manipulated embryo; tracing shows axon projections from the right eye to the left tectum; calcium imaging shows increased activity on the injected side of a unilaterally manipulated embryo. (f) A heatmap from an omics analysis. (g) Western blot results from a co‐immunoprecipitation experiment. (h) Results comparing excitatory post‐synaptic current (EPSC) recordings from a control animal (blue) and a manipulated sibling (red). (i) Sound pulses from an advertisement vocal call
	FIGURE 2 Schematic representations of the developing Xenopus brain. Lateral views of the Xenopus brain (anterior to the left and dorsal at the top) at NF (Nieuwkoop and Faber) stages 38 (a), 42 (b), 46 (c), and 50 (d). Colors demarcate the developing telencephalon (blue), hypothalamus (purple), diencephalon (green), mesencephalon (pink), midbrain‐hindbrain boundary (MHB, gray), and rhombencephalon (yellow). Images are representative of X. laevis and X. tropicalis. See text for anatomical references. Xenopus stages according to Nieuwkoop and Faber (1994). a, alar; b, basal; DP, dorsal pallium; Hab, habenula; LGE, lateral ganglionic eminence; LP, lateral pallium; MGE, medial ganglionic eminence; MHB, midbrain‐hindbrain boundary; MP, medial pallium; OB, olfactory bulb; P, pallium; p, prosomere; r, rhombomere; SP, subpallium; VP, ventral pallium
	FIGURE 3 Schematic representations of Xenopus forebrain sections during development. Cross‐sectional views of the Xenopus telencephalon (dorsal at the top) at NF stages 38 (a), 42 (b), 46 (c), and 50 (d). Images are representative of X. laevis and X. tropicalis. See text for anatomical references. Xenopus stages according to Nieuwkoop and Faber (1994). Abbreviations as in Figure 2, and MZ, marginal zone; SVZ, subventricular zone; V, ventricle; VZ, ventricular zone
	FIGURE 4 Schematic representations of Xenopus stage 38 expression patterns. Lateral (a, b) and telencephalon cross‐sectional (c, d) views showing expression domains of key patterning genes at NF stage 38. Stripes indicate co‐expression of genes. See key in figure for color coding. Expression patterns are highly conserved between frogs and mammals (see text for references). Xenopus stage according to Nieuwkoop and Faber (1994). Dotted gray line in A indicates sectional plane shown in (c) and (d). Abbreviations as in Figures 2 and 3

References [+] :

Ablondi, Fluorescent Calcium Imaging and Subsequent In Situ Hybridization for Neuronal Precursor Characterization in Xenopus laevis. 2020, Pubmed, Xenbase