XB-ART-57657Genesis January 1, 2021; 59 (1-2): e23404.
Using Xenopus to analyze neurocristopathies like Kabuki syndrome.
Neurocristopathies are human congenital syndromes that arise from defects in neural crest (NC) development and are typically associated with malformations of the craniofacial skeleton. Genetic analyses have been very successful in identifying pathogenic mutations, however, model organisms are required to characterize how these mutations affect embryonic development thereby leading to complex clinical conditions. The African clawed frog Xenopus laevis provides a broad range of in vivo and in vitro tools allowing for a detailed characterization of NC development. Due to the conserved nature of craniofacial morphogenesis in vertebrates, Xenopus is an efficient and versatile system to dissect the morphological and cellular phenotypes as well as the signaling events leading to NC defects. Here, we review a set of techniques and resources how Xenopus can be used as a disease model to investigate the pathogenesis of Kabuki syndrome and neurocristopathies in a wider sense.
PubMed ID: 33351273
Article link: Genesis
Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: chd7 col2a1 kdm6a kmt2d pax3 snai1 snai2 sox10 sox9 twist1
Disease Ontology terms: CHARGE syndrome
OMIMs: KABUKI SYNDROME 1; KABUK1
Article Images: [+] show captions
|FIGURE 1. Kabuki phenotype. Sketch depicting the typical Kabuki features (left) including large prominent ears, arched eyebrows, thick, eyelashes, long palpebral fissures, eversion of lateral third of lower eyelids and short nasal columella. The right shows an artistic sketch of a Kabuki mask|
|FIGURE 2. Overview of the different stages of Xenopus NC development. Embryos were analyzed for pax3 (Stage 14), snail2(Stage 18), twist (Stage 26), and sox9 (Stage 30) expression by in situ hybridization. Nieuwkoop and Faber stages of the analyzed embryos are indicated in brackets. Arrowheads and brackets indicate mandibular (m), hyoid (h), and branchial (b) neural crest streams. NPB: neural plate border. Collagen Type II expression was analyzed by immunostaining at stage 44 to visualize cranial cartilage structures. Cb, ceratobranchial; Ch, ceratohyal; Ir, infrarostral; Me, Meckel's cartilage; Qu, quadrate|
|FIGURE 3. NC transplants and explants. (a) Embryo transplanted with NC cells marked by GFP expression (a, brightfield; a', fluorescent image). (b) Explanted NC cells expressing membrane targeted GFP (mGFP) and H2B‐mcherry to label the nucleus. (b) shows an image at the start of the experiment, (b') 5 hr after explantation. (c) Single migrating NC cell expressing mGFP and H2B‐cherry. The migration track over 30 min is indicated by a dashed line|