ZFIN ID: ZDB-PUB-140710-1
Ncor2 is required for hematopoietic stem cell emergence by inhibiting Fos signaling in zebrafish
Wei, Y., Ma, D., Gao, Y., Zhang, C., Wang, L., Liu, F.
Date: 2014
Source: Blood   124(10): 1578-85 (Journal)
Registered Authors: Gao, Ya, Liu, Feng, Ma, Dongyuan, Wang, Lu, Wei, Yonglong, Zhang, Chunxia
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation/genetics
  • Down-Regulation/genetics
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Hematopoiesis/genetics*
  • Hematopoietic Stem Cells/physiology*
  • Nuclear Receptor Co-Repressor 2/physiology*
  • Oncogene Proteins v-fos/genetics*
  • Oncogene Proteins v-fos/metabolism
  • Signal Transduction/genetics
  • Vascular Endothelial Growth Factor D/genetics*
  • Vascular Endothelial Growth Factor D/metabolism
  • Zebrafish*/embryology
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 25006126 Full text @ Blood
Nuclear receptor co-repressors (Ncor) are important for developmental and homeostatic processes in vertebrates, which exert transcriptional repression by coordinating with histone deacetylases (Hdac). However, little is known about their roles in definitive hematopoiesis. Here, we show that, in zebrafish, ncor2 is required for hematopoietic stem cell (HSC) development by repressing fos-vegfd signaling. ncor2 is specifically expressed in the aorta-gonad-mesonephros (AGM) region in zebrafish embryos. ncor2 deficiency reduced the population of both HSCs in the AGM region and T cells in the thymus. Mechanistically, ncor2 knockdown upregulated fos transcription by modulating the acetylation level in the fos promoter region, which then enhanced Vegfd signaling. Consequently, the augmented Vegfd signaling induced Notch signaling to promote the arterial endothelial fate, therefore possibly repressing the hemogenic endothelial specification which is a prerequisite for HSC emergence. Thus, our findings identify a novel regulatory mechanism for Ncor2 through Fos-Vegfd-Notch signaling cascade during HSC development in zebrafish embryos.