<i>Xenopus</i>: An ideal system for chemical genetics

Wheeler, Grant N.; Liu, Karen

doi:10.1002/dvg.22009

Cited by 30 publications

(18 citation statements)

References 76 publications

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“…X. tropicalis is quickly becoming a relevant amphibian model species because of the notable advantages that this species offers for research (66,67). Nevertheless, it is surprising that the existence of three sex chromosomes has not been revealed before.…”

Section: Discussionmentioning

confidence: 99%

Coexistence of Y, W, and Z sex chromosomes in Xenopus tropicalis

Roco

Olmstead

Degitz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Homomorphic sex chromosomes and rapid turnover of sex-determining genes can complicate establishing the sex chromosome system operating in a given species. This difficulty exists in Xenopus tropicalis, an anuran quickly becoming a relevant model for genetic, genomic, biochemical, and ecotoxicological research. Despite the recent interest attracted by this species, little is known about its sex chromosome system. Direct evidence that females are the heterogametic sex, as in the related species Xenopus laevis, has yet to be presented. Furthermore, X. laevis' sex-determining gene, DM-W, does not exist in X. tropicalis, and the sex chromosomes in the two species are not homologous. Here we identify X. tropicalis' sex chromosome system by integrating data from (i) breeding sex-reversed individuals, (ii) gynogenesis, (iii) triploids, and (iv) crosses among several strains. Our results indicate that at least three different types of sex chromosomes exist: Y, W, and Z, observed in YZ, YW, and ZZ males and in ZW and WW females. Because some combinations of parental sex chromosomes produce unisex offspring and other distorted sex ratios, understanding the sex-determination systems in X. tropicalis is critical for developing this flexible animal model for genetics and ecotoxicology.

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Section: Discussionmentioning

confidence: 99%

Coexistence of Y, W, and Z sex chromosomes in Xenopus tropicalis

Roco

Olmstead

Degitz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The Brändli lab reported employing CRISPR/Cas9 for modeling rare inherited human diseases and for subsequent phenotypic drug screening (Schmitt et al ., ; Wheeler and Liu, ). While we believe this approach to be extremely strong, current tumor GEXM do not allow for high‐throughput phenotypic drug discovery screening due to latency until tumor development, disfavoring efficient array‐based screening methods.…”

Section: Applications Of Xtropicalis Tumor Modelsmentioning

confidence: 99%

TALENs and CRISPR/Cas9 fuel genetically engineered clinically relevant Xenopus tropicalis tumor models

Naert

Nieuwenhuysen

Vleminckx

2017

Genesis

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The targeted nuclease revolution (TALENs, CRISPR/Cas9) now allows Xenopus researchers to rapidly generate custom on-demand genetic knockout models. These novel methods to perform reverse genetics are unprecedented and are fueling a wide array of human disease models within the aquatic diploid model organism Xenopus tropicalis (X. tropicalis). This emerging technology review focuses on the tools to rapidly generate genetically engineered X. tropicalis models (GEXM), with a focus on establishment of genuine genetic and clinically relevant cancer models. We believe that due to particular advantageous characteristics, outlined within this review, GEXM will become a valuable alternative animal model for modeling human cancer. Furthermore, we provide perspectives of how GEXM will be used as a platform for elucidation of novel therapeutic targets and for preclinical drug validation. Finally, we also discuss some future prospects on how the recent expansions and adaptations of the CRISPR/Cas9 toolbox might influence and push forward X. tropicalis cancer research.

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“…Xenopus has emerged as an effective tool to chemically screen for novel mechanisms governing specific developmental events [93]. This aquatic species is an ideal organism for such experiments since it develops ex utero and fertilized embryos can be obtained simultaneously in large numbers by in vitro fertilization.…”

Section: Introductionmentioning

confidence: 99%

Using frogs faces to dissect the mechanisms underlying human orofacial defects

Dickinson

2016

Seminars in Cell & Developmental Biology

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In this review I discuss how Xenopus laevis is an effective model to dissect the mechanisms underlying orofacial defects. This species has been particularly useful in studying the understudied structures of the developing face including the embryonic mouth and primary palate. The embryonic mouth is the first opening between the foregut and the environment and is critical for adult mouth development. The final step in embryonic mouth formation is the perforation of a thin layer of tissue covering the digestive tube called the buccopharyngeal membrane. When this tissue does not perforate in humans it can pose serious health risks for the fetus and child. The primary palate forms just dorsal to the embryonic mouth and in non-amniotes it functions as the roof of the adult mouth. Defects in the primary palate result in a median oral cleft that appears similar across the vertebrates. In humans, these median clefts are often severe and surgically difficult to repair. Xenopus has several qualities that make it advantageous for craniofacial research. The free living embryo has an easily accessible face and we have also developed several new tools to analyze the development of the region. Further, Xenopus is readily amenable to chemical screens allowing us to uncover novel gene-environment interactions during orofacial development, as well as to define underlying mechanisms governing such interactions. In conclusion, we are utilizing Xenopus in new and innovative ways to contribute to craniofacial research.

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Xenopus: An ideal system for chemical genetics

Cited by 30 publications

References 76 publications

Coexistence of Y, W, and Z sex chromosomes in Xenopus tropicalis

Coexistence of Y, W, and Z sex chromosomes in Xenopus tropicalis

TALENs and CRISPR/Cas9 fuel genetically engineered clinically relevant Xenopus tropicalis tumor models

Using frogs faces to dissect the mechanisms underlying human orofacial defects

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