Dyrk1a is required for craniofacial development in Xenopus laevis.

Autor: Johnson HK; Department of Biology, Virginia Commonwealth University, Richmond, VA, USA., Wahl SE; Department of Biology, Virginia Commonwealth University, Richmond, VA, USA., Sesay F; Department of Internal Medicine, Division of Hematology, Oncology and Palliative Care, Virginia Commonwealth University, Richmond, VA, USA., Litovchick L; Department of Internal Medicine, Division of Hematology, Oncology and Palliative Care, Virginia Commonwealth University, Richmond, VA, USA; Massey Comprehensive Cancer Center, Richmond, VA, USA., Dickinson AJ; Department of Biology, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: ajdickinson@vcu.edu.
Jazyk: angličtina
Zdroj: Developmental biology [Dev Biol] 2024 Jul; Vol. 511, pp. 63-75. Date of Electronic Publication: 2024 Apr 15.
DOI: 10.1016/j.ydbio.2024.04.004
Abstrakt: Loss of function variations in the dual specificity tyrosine-phosphorylation-regulated kinase 1 A (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.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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