PUBLICATION

Overexpression of DYRK1A, a Down Syndrome Candidate gene, Impairs Primordial Germ Cells Maintenance and Migration in zebrafish

Authors

Liu, Y., Lin, Z., Liu, M., Wang, H., Sun, H.

ID

ZDB-PUB-171113-5

Date

2017

Source

Scientific Reports 7: 15313 (Journal)

Registered Authors

Keywords

none

MeSH Terms

Germ Cells/metabolism*
Humans
Embryonic Development
Zebrafish Proteins/biosynthesis*
Zebrafish Proteins/genetics
Animals
Cell Movement*
K562 Cells
Protein-Tyrosine Kinases/biosynthesis*
Protein-Tyrosine Kinases/genetics
Protein Serine-Threonine Kinases/biosynthesis*
Protein Serine-Threonine Kinases/genetics
Animals, Genetically Modified
Down Syndrome*
Embryo, Nonmammalian/metabolism*
Zebrafish

(all 16)

PubMed

29127398 Full text @ Sci. Rep.

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 of DYRK1A has potential effect on primordial germ cells (PGCs) development. Human and zebrafish DYRK1A 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 of DYRK1A in PGCs development during embryogenesis. We injected DYRK1A mRNA into embryos and detected the PGCs marker gene vasa and nanos1. Results showed depletion in numbers and disordering migration of PGCs in human or zebrafish DYRK1A overexpressed zebrafish embryos. Quantitative proteome analysis indicated that embryonic proteins were significantly altered in DYRK1A overexpressed embryos. Of note, ca15b and piwil1, two identified critical factors for PGCs development, showed ectopic expression induced by overexpressed DYRK1A. In brief, we demonstrate that overexpression of DYRK1A, 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.

Genes / Markers

Figures