期刊
DEVELOPMENT
卷 147, 期 21, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.189290
关键词
DYRK1A; Ciliogenesis; Autism; Down Syndrome; Microtubules; Spindle
资金
- National Institute of Mental Health [1R21MH112158-01]
- National Institute of General Medical Sciences [R35GM127069]
- National Institutes of Health [1U01MH115747-01A1]
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, individuals with putative lossof-function variants in DYRK1A exhibit microcephaly, intellectual disability, developmental delay and/or 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 used 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.
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