Overexpression of DYRK1A, a Down Syndrome Candidate gene, Impairs Primordial Germ Cells Maintenance and Migration in zebrafish. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Liu, Yanyan; Lin, Ziyuan; Liu, Mingfeng; Wang, He; Sun, Huaqin
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-15730-w
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract DYRK1A, located on chromosome 21, is a major candidate gene of Down syndrome (DS, trisomy21), and its overexpression is associated with abnormal phenotype of Down syndrome patients. The defects of gonads and germ cells in Down Syndrome suggest that overexpression ofDYRK1A has potential effect on primordial germ cells (PGCs) development. Human and zebrafishDYRK1A protein sequence possess 75.6% similarity and same function domains, suggesting the evolutional conservation. Here, we used zebrafish model to detect the definite role of excessive expression ofDYRK1A in PGCs development during embryogenesis. We injectedDYRK1A mRNA into embryos and detected the PGCs marker genevasa andnanos1 . Results showed depletion in numbers and disordering migration of PGCs in human or zebrafishDYRK1A overexpressed zebrafish embryos. Quantitative proteome analysis indicated that embryonic proteins were significantly altered inDYRK1A overexpressed embryos. Of note, ca15b and piwil1, two identified critical factors for PGCs development, showed ectopic expression induced by overexpressedDYRK1A . In brief, we demonstrate that overexpression ofDYRK1A, a candidate gene of Down's syndrome, impairs PGCs development during early embryogenesis by altering key factors in embryos. Importantly, our work may provide a conceivable mechanism for the gonads and germ cells defects of Down syndrome patients.