論文 - 詳細
| RRC ID | 87489 |
|---|---|
| 著者 | 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. |
| タイトル | DDX24 spatiotemporally orchestrates VEGF and Wnt signaling during developmental angiogenesis. |
| ジャーナル | Proc Natl Acad Sci U S A |
| 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. |
| 巻・号 | 122(19) |
| ページ | e2417445122 |
| 公開日 | 2025-5-13 |
| DOI | 10.1073/pnas.2417445122 |
| PMID | 40339127 |
| PMC | PMC12088455 |
| MeSH | Angiogenesis Animals DEAD-box RNA Helicases* / genetics DEAD-box RNA Helicases* / metabolism Endothelial Cells / metabolism Gene Expression Regulation, Developmental Neovascularization, Physiologic* / genetics Vascular Endothelial Growth Factor A* / genetics Vascular Endothelial Growth Factor A* / metabolism Vascular Endothelial Growth Factor Receptor-2 / genetics Vascular Endothelial Growth Factor Receptor-2 / metabolism Wnt Signaling Pathway* Zebrafish / embryology Zebrafish / genetics Zebrafish / metabolism Zebrafish Proteins* / genetics Zebrafish Proteins* / metabolism |
| IF | 9.412 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | Tg(kdrl:NLS-Eos)ncv6Tg |