ZFIN ID: ZDB-PUB-130108-1
Zebrafish scube1 [signal peptide-CUB (complement protein C1r/C1s, Uegf, and Bmp1)-EGF domain-containing protein 1] Is Involved in Primitive Hematopoiesis
Tsao, K.C., Tu, C.F., Lee, S.J., and Yang, R.B.
Date: 2013
Source: The Journal of biological chemistry   288(7): 5017-5026 (Journal)
Registered Authors: Lee, Shyh-Jye
Keywords: bone morphogenic protein (BMP), cell surface protein, hematopoiesis, signal transduction, zebrafish, primitive hematopoiesis
MeSH Terms:
  • Animals
  • Bone Morphogenetic Proteins/metabolism
  • Calcium-Binding Proteins/genetics*
  • Calcium-Binding Proteins/physiology*
  • Cell Membrane/metabolism
  • DNA, Complementary/metabolism
  • Epidermal Growth Factor/metabolism*
  • Erythrocytes/metabolism
  • Gene Expression Regulation*
  • HEK293 Cells
  • Hematopoiesis/physiology*
  • Humans
  • In Situ Hybridization
  • Models, Genetic
  • Molecular Sequence Data
  • Oligonucleotides/genetics
  • Protein Structure, Tertiary
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/physiology*
PubMed: 23271740 Full text @ J. Biol. Chem.

Scube1 (signal peptide-CUB-EGF domain-containing protein 1), the founding member of a novel secreted and cell-surface SCUBE protein family, is expressed predominantly in various developing tissues in mice. However, its function in primitive hematopoiesis remains unknown. In this study, we identified and characterized zebrafish scube1 and analyzed its function by injecting antisense morpholino oligonucleotide (MO) into embryos. Whole-mount in situ hybridization revealed that zebrafish scube1 mRNA is maternally expressed and widely distributed during early embryonic development. Knockdown of scube1 by MO downregulated the expression of marker genes associated with early primitive hematopoietic precursors (scl) and erythroid (gata1 and hbbe1), as well as early (pu.1) and late (mpo and l-plastin) myelomonocytic lineages. However, the expression of an early endothelial marker fli1a and vascular morphogenesis appeared normal in scube1 morphants. Overexpression of bone morphogenetic protein (bmp) rescued the expression of scl in the posterior lateral mesoderm during early primitive hematopoiesis in scube1 morphants. Biochemical and molecular analysis revealed that Scube1 could be a BMP co-receptor to augment BMP signaling. Our results suggest that scube1 is critical for and functions at the top of the regulatory hierarchy of primitive hematopoiesis by modulating BMP activity during zebrafish embryogenesis.