Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-57345
Genesis January 1, 2021; 59 (1-2): e23394.

Using an aquatic model, Xenopus laevis, to uncover the role of chromodomain 1 in craniofacial disorders.

Wyatt BH , Raymond TO , Lansdon LA , Darbro BW , Murray JC , Manak JR , Dickinson AJG .


Abstract
The chromodomain family member chromodomain 1 (CHD1) has been shown to have numerous critical molecular functions including transcriptional regulation, splicing, and DNA repair. Complete loss of function of this gene is not compatible with life. On the other hand, missense and copy number variants of CHD1 can result in intellectual disabilities and craniofacial malformations in human patients including cleft palate and Pilarowski-Bjornsson Syndrome. We have used the aquatic developmental model organism Xenopus laevis, to determine a specific role for Chd1 in such cranioafcial disorders. Protein and gene knockdown techniques in Xenopus, including antisense oligos and mosaic Crispr/Cas9-mediated mutagenesis, recapitulated the craniofacial defects observed in humans. Further analysis indicated that embryos deficient in Chd1 had defects in cranial neural crest development and jaw cartilage morphology. Additionally, flow cytometry and immunohistochemistry revealed that decreased Chd1 resulted in increased in apoptosis in the developing head. Together, these experiments demonstrate that Chd1 is critical for fundamental processes and cell survival in craniofacial development. We also presented evidence that Chd1 is regulated by retinoic acid signaling during craniofacial development. Expression levels of chd1 mRNA, specifically in the head, were increased by RAR agonist exposure and decreased upon antagonist treatment. Subphenotypic levels of an RAR antagonist and Chd1 morpholinos synergized to result in orofacial defects. Further, RAR DNA binding sequences (RAREs) were detected in chd1 regulatory regions by bioinformatic analysis. In summary, by combining human genetics and experiments in an aquatic model we now have a better understanding of the role of CHD1 in craniofacial disorders.

PubMed ID: 32918369
Article link: Genesis
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aldh1a2 chd1 rarg slc45a2 tfap2a
GO keywords: neural crest cell development [+]
Antibodies: Casp3 Ab1
Morpholinos: aldh1a2 MO1 chd1 MO1 chd1 MO2
gRNAs referenced: chd1 gRNA1 slc45a2 gRNA2

Disease Ontology terms: orofacial cleft [+]
OMIMs: CLEFT SOFT PALATE [+]
Phenotypes: Xla Wt + BMS453 (Fig. 7 a b) [+]

Article Images: [+] show captions