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XB-ART-60673
Dev Biol 2024 Jul 01;511:63-75. doi: 10.1016/j.ydbio.2024.04.004.
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Dyrk1a is required for craniofacial development in Xenopus laevis.

Johnson HK , Wahl SE , Sesay F , Litovchick L , Dickinson AJ .


Abstract
Loss of function variations in the dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene are associated with craniofacial malformations in humans. Here we characterized the effects of deficient DYRK1A in craniofacial development using a developmental model, Xenopus laevis. Dyrk1a mRNA and protein were expressed throughout the developing head and both were enriched in the branchial arches which contribute to the face and jaw. Consistently, reduced Dyrk1a function, using dyrk1a morpholinos and pharmacological inhibitors, resulted in orofacial malformations including hypotelorism, altered mouth shape, slanted eyes, and narrower face accompanied by smaller jaw cartilage and muscle. Inhibition of Dyrk1a function resulted in misexpression of key craniofacial regulators including transcription factors and members of the retinoic acid signaling pathway. Two such regulators, sox9 and pax3 are required for neural crest development and their decreased expression corresponds with smaller neural crest domains within the branchial arches. Finally, we determined that the smaller size of the faces, jaw elements and neural crest domains in embryos deficient in Dyrk1a could be explained by increased cell death and decreased proliferation. This study is the first to provide insight into why craniofacial birth defects might arise in humans with variants of DYRK1A.

PubMed ID: 38621649
Article link: Dev Biol


Species referenced: Xenopus laevis
Genes referenced: alx4 dyrk1a dyrk1a.2 gapdh gbx2 pax3 rarg rpl31 sox10 sox9
GO keywords: head development [+]
Morpholinos: dyrk1a MO1

Disease Ontology terms: intellectual disability [+]
OMIMs: DOWN SYNDROME [+]