ZFIN ID: ZDB-PUB-180223-60
Ribosome biogenesis protein Urb2 regulates hematopoietic stem cells development via P53 pathway in zebrafish
Cai, P., Mao, X., Zhao, J., Luo, L.
Date: 2018
Source: Biochemical and Biophysical Research Communications   497(2): 776-782 (Journal)
Registered Authors: Luo, Lingfei
Keywords: Hematopoietic stem cells, P53, Ribosome biogenesis, Urb2, Zebrafish
MeSH Terms:
  • Animals
  • Apoptosis
  • CRISPR-Cas Systems
  • Cell Cycle
  • Gene Targeting
  • Hematopoiesis*
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism
  • Mutation
  • Signal Transduction
  • Tumor Suppressor Protein p53/metabolism*
  • Zebrafish/genetics
  • Zebrafish/physiology*
PubMed: 29470984 Full text @ Biochem. Biophys. Res. Commun.
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ABSTRACT
Ribosome biogenesis is a significant process in cells. Dysfunction in this process will result in the defects of protein synthesis and consequently cause the development of specific diseases called ribosomopathies. Mutations in ribosome biogenesis protein Rps19, Rpl5, or Rpl11 can lead to hematopoietic defects in human, thus triggering the disease Diamond Blackfan anemia. However, the regulatory mechanisms of ribosome biogenesis in hematopoiesis remain incompletely understood. In this study, we describe a zebrafish mutant cq42, which carries a nonsense mutation in the gene that encodes ribosome biogenesis 2 homolog (Urb2). Urb2 is strongly expressed in the caudal hematopoietic tissue (CHT) during hematopoietic stem cells (HSCs) expanding. Molecular characterization of urb2cq42 larvae suggest that urb2 deficiency notably decrease the population of HSCs in CHT and early T cells in thymus. Further analysis shows that compromised cell proliferation and superfluous apoptosis are observed in the CHT of urb2cq42 mutant. P53 pathway is upregulated in the urb2cq42 larvae and loss-of-function of P53 can fully rescue the hematopoietic defects in urb2cq42 mutant. These data demonstrate that urb2 is essential for HSCs development through the regulation of P53 pathway.
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