PUBLICATION
The pro-inflammatory signalling regulator Stat4 promotes vasculogenesis of great vessels derived from endothelial precursors
- Authors
- Meng, Z.Z., Liu, W., Xia, Y., Yin, H.M., Zhang, C.Y., Su, D., Yan, L.F., Gu, A.H., Zhou, Y.
- ID
- ZDB-PUB-170304-2
- Date
- 2017
- Source
- Nature communications 8: 14640 (Journal)
- Registered Authors
- Zhou, Yong
- Keywords
- Cell growth, Differentiation, Disease model
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Arteries/abnormalities
- Arteries/growth & development*
- Branchial Region/blood supply
- Branchial Region/growth & development
- Cardiovascular Diseases/genetics*
- Cell Differentiation/genetics
- Cell Proliferation/genetics
- Embryo, Nonmammalian
- Endothelial Cells/physiology
- Gene Expression Regulation, Developmental*
- Gene Knockdown Techniques
- Histone Deacetylases/genetics
- Histone Deacetylases/metabolism
- Homeobox Protein Nkx-2.5/genetics
- Homeobox Protein Nkx-2.5/metabolism
- Mesoderm/cytology
- Mesoderm/growth & development
- Models, Animal
- Morphogenesis/genetics*
- Morpholinos/genetics
- STAT4 Transcription Factor/genetics
- STAT4 Transcription Factor/metabolism
- STAT4 Transcription Factor/physiology*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 28256502 Full text @ Nat. Commun.
Citation
Meng, Z.Z., Liu, W., Xia, Y., Yin, H.M., Zhang, C.Y., Su, D., Yan, L.F., Gu, A.H., Zhou, Y. (2017) The pro-inflammatory signalling regulator Stat4 promotes vasculogenesis of great vessels derived from endothelial precursors. Nature communications. 8:14640.
Abstract
Vasculogenic defects of great vessels (GVs) are a major cause of congenital cardiovascular diseases. However, genetic regulators of endothelial precursors in GV vasculogenesis remain largely unknown. Here we show that Stat4, a transcription factor known for its regulatory role of pro-inflammatory signalling, promotes GV vasculogenesis in zebrafish. We find stat4 transcripts highly enriched in nkx2.5+ endothelial precursors in the pharynx and demonstrate that genetic ablation of stat4 causes stenosis of pharyngeal arch arteries (PAAs) by suppressing PAAs 3-6 angioblast development. We further show that stat4 is a downstream target of nkx2.5 and that it autonomously promotes proliferation of endothelial precursors of the mesoderm. Mechanistically, stat4 regulates the emerging PAA angioblasts by inhibiting the expression of hdac3 and counteracting the effect of stat1a. Altogether, our study establishes a role for Stat4 in zebrafish great vessel development, and suggests that Stat4 may serve as a therapeutic target for GV defects.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping