PUBLICATION
DDX24 spatiotemporally orchestrates VEGF and Wnt signaling during developmental angiogenesis
- Authors
- Chen, F., Deng, Z., Wang, X., Liu, Y., Zhao, K., Zhang, Y., He, S., Ran, R., Dong, Y., Guo, S., Zhou, Y., Zhou, B., Pang, P., Ge, W., Liu, C., Shan, H., He, H.
- ID
- ZDB-PUB-250510-3
- Date
- 2025
- Source
- Proceedings of the National Academy of Sciences of the United States of America 122: e2417445122e2417445122 (Journal)
- Registered Authors
- Ge, Wei, He, Huanhuan
- Keywords
- DEAD-box helicase 24, VEGF, developmental angiogenesis, endothelial cells, spatial transcriptomics
- MeSH Terms
-
- Angiogenesis
- Animals
- Vascular Endothelial Growth Factor A*/genetics
- Vascular Endothelial Growth Factor A*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Vascular Endothelial Growth Factor Receptor-2/genetics
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- DEAD-box RNA Helicases*/genetics
- DEAD-box RNA Helicases*/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism
- Endothelial Cells/metabolism
- Wnt Signaling Pathway*
- Gene Expression Regulation, Developmental
- Neovascularization, Physiologic*/genetics
- PubMed
- 40339127 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Chen, F., Deng, Z., Wang, X., Liu, Y., Zhao, K., Zhang, Y., He, S., Ran, R., Dong, Y., Guo, S., Zhou, Y., Zhou, B., Pang, P., Ge, W., Liu, C., Shan, H., He, H. (2025) DDX24 spatiotemporally orchestrates VEGF and Wnt signaling during developmental angiogenesis. Proceedings of the National Academy of Sciences of the United States of America. 122:e2417445122e2417445122.
Abstract
Vascular development is a precisely controlled process, yet how it is spatiotemporally orchestrated remains enigmatic. We previously identified DEAD-box RNA helicase 24 (DDX24) as a pathogenic gene for multiorgan vascular anomalies. Here, we show that DDX24 is expressed in the endothelium during embryonic angiogenesis in zebrafish. DDX24 deficiency causes intersegmental vessel hyperbranching in the trunk, but inhibits central artery angiogenesis in the brain. Mechanistically, DDX24 deficiency enhances VEGFR2 expression by direct binding to its mRNA in nonbrain endothelial cells (ECs), while suppressing GPR124/RECK-mediated Wnt signaling in brain ECs. Additionally, spatial transcriptome analysis profiles DDX24-mediated crosstalk between ECs and neighboring cells. Finally, pharmacological targeting of these two pathways in a temporal manner can rescue the phenotypes induced by DDX24 deficiency. Overall, our findings highlight an essential role for DDX24 in the spatiotemporal regulation of developmental angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping