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XB-ART-56785
Front Physiol January 1, 2020; 11 75.

Modeling Bainbridge-Ropers Syndrome in Xenopus laevis Embryos.

Lichtig H , Artamonov A , Polevoy H , Reid CD , Bielas SL , Frank D .


Abstract
The Additional sex combs-like (ASXL1-3) genes are linked to human neurodevelopmental disorders. The de novo truncating variants in ASXL1-3 proteins serve as the genetic basis for severe neurodevelopmental diseases such as Bohring-Opitz, Shashi-Pena, and Bainbridge-Ropers syndromes, respectively. The phenotypes of these syndromes are similar but not identical, and include dramatic craniofacial defects, microcephaly, developmental delay, and severe intellectual disability, with a loss of speech and language. Bainbridge-Ropers syndrome resulting from ASXL3 gene mutations also includes features of autism spectrum disorder. Human genomic studies also identified missense ASXL3 variants associated with autism spectrum disorder, but lacking more severe Bainbridge-Ropers syndromic features. While these findings strongly implicate ASXL3 in mammalian brain development, its functions are not clearly understood. ASXL3 protein is a component of the polycomb deubiquitinase complex that removes mono-ubiquitin from Histone H2A. Dynamic chromatin modifications play important roles in the specification of cell fates during early neural patterning and development. In this study, we utilize the frog, Xenopus laevis as a simpler and more accessible vertebrate neurodevelopmental model system to understand the embryological cause of Bainbridge-Ropers syndrome. We have found that ASXL3 protein knockdown during early embryo development highly perturbs neural cell fate specification, potentially resembling the Bainbridge-Ropers syndrome phenotype in humans. Thus, the frog embryo is a powerful tool for understanding the etiology of Bainbridge-Ropers syndrome in humans.

PubMed ID: 32132929
Article link: Front Physiol

Genes referenced: acss2.1 acss2.2 ag1 asxl1 asxl2 asxl3 cdx1 cdx2 cdx4 chrd.1 egr2 foxd1 foxd3 foxg1 gsc h2ac21 hesx1 hoxa2 hoxb1 hoxb3 hoxb4 hoxb5 hoxd1 meis3 myod1 ncam1 nog not nrp1 odc1 osr1 osr2 otx2 snai2 tbxt tub tubb2b twist1 ventx2.2
GO keywords: neural crest formation
Morpholinos: asxl3 MO1

OMIMs: BAINBRIDGE-ROPERS SYNDROME; BRPS

Article Images: [+] show captions
References [+] :
Aamar, Xenopus Meis3 protein forms a hindbrain-inducing center by activating FGF/MAP kinase and PCP pathways. 2004, Pubmed, Xenbase


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