Return to search results Title: Neurodevelopmental disorder risk gene DYRK1A is required for ciliogenesis and brain size in Xenopus embryos

Summary

DYRK1A (dual specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A) is a high confidence autism risk gene that encodes a conserved kinase. In addition to autism, patients with putative loss of function variants in DYRK1A exhibit microcephaly, intellectual disability, developmental delay, and congenital anomalies of the kidney and urinary tract. DYRK1A is also located within the critical region for Down syndrome; therefore, understanding the role of DYRK1A in brain development is crucial for understanding the pathobiology of multiple developmental disorders. To characterize the function of this gene, we leveraged the diploid frog, Xenopus tropicalis. We discover that Dyrk1a is expressed in ciliated tissues, localizes to ciliary axonemes and basal bodies, and is required for ciliogenesis. We also demonstrate that Dyrk1a localizes to mitotic spindles and that its inhibition leads to decreased forebrain size, abnormal cell cycle progression, and cell death during brain development. These findings provide hypotheses about potential mechanisms of pathobiology and underscore the utility of X. tropicalis as a model system for understanding neurodevelopmental disorders.

Contributors: Arthur Willsey, Helen Willsey, A Willsey

Experiment Type: 3 replicates each of 3 pooled dissected stage 46 X. tropicalis brains, either uninjected or bilaterally injected with CRISPR reagents targeting dyrk1a at the 2 cell stage. Trizol extracted RNA, low yield library preparation, and Illumina sequencing.

Experiment Reagents: dyrk1a.


Article: XB-ART-57038, PubMed

Source: NCBI GEO, Xenbase Download

Sample	View		GSMs	Assay Type
brain - NF46 GSM4504555  GSM4504556  GSM4504557  RNA-Seq Xtr   [-] [+] Background: Xtr.Outbred Conditions: Tissue Assay Stages ChIP Antibody brain NF stage 46      brain + dyrk1a CRISPR - NF46 DEG GSM4504552  GSM4504553  GSM4504554  RNA-Seq Xtr   [-] [+] Background: Xtr.Outbred Manipulations: Manipulation Type Reagent Target Gene Stage Treatment Area CRISPR dyrk1a dyrk1a NF stage 2 (2-cell) blastomere Conditions: Tissue Assay Stages ChIP Antibody brain NF stage 46

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