DDX24 spatiotemporally orchestrates VEGF and Wnt signaling during developmental angiogenesis
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.
Authors
- Rensen Ran (ORCID: https://orcid.org/0009-0001-9863-4735)
- Pengfei Pang
- Wei Ge (ORCID: https://orcid.org/0000-0002-4296-1585)
- Fangbin Chen (ORCID: https://orcid.org/0000-0002-1705-350X)
- Simeng He (ORCID: https://orcid.org/0000-0002-3855-8005)
- Huanhuan He (ORCID: https://orcid.org/0000-0002-5903-0840)
- Yingying Dong (ORCID: https://orcid.org/0000-0002-2865-5020)
- Shuang Guo (ORCID: https://orcid.org/0000-0002-5636-5506)
- Kuaile Zhao (ORCID: https://orcid.org/0000-0001-8663-2874)
- Yue Zhang (ORCID: https://orcid.org/0000-0001-7856-7451)
- Chang Liu (ORCID: https://orcid.org/0000-0002-5717-3370)
- Xiaoming Wang (ORCID: https://orcid.org/0000-0003-0679-9768)
- Yuxuan Liu (ORCID: https://orcid.org/0000-0003-4426-9290)
- Hong Shan (ORCID: https://orcid.org/0000-0002-8896-5813)
- Zihou Deng (ORCID: https://orcid.org/0009-0007-2743-668X)
- Bin Zhou (ORCID: https://orcid.org/0000-0001-7596-5737)
- Yitong Zhou
Institutions
- Sun Yat-sen University (CN)
- Shanxi Medical University (CN)
- University of Macau (MO)
- Huazhong Agricultural University (CN)
- Wuhan University (CN)
- Fifth Affiliated Hospital of Sun Yat-sen University (CN)
- Botswana Geoscience Institute (BW)
- BGI Research (CN)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-05-08
- DOI
- https://doi.org/10.1073/pnas.2417445122
- Citations
- 3
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 2.81
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province
- National Key Research and Development Program of China Stem Cell and Translational Research