DDX24 spatiotemporally orchestrates VEGF and Wnt signaling during developmental angiogenesis
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (17)
Fangbin Chen
Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University
Zhaohua Deng
Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University
Xiaoming Wang
Yuxuan Liu
Kaichen Zhao
College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University
Yue Zhang
Simeng He
Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University
Rensen Ran
State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital
Yingying Dong
Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University
Shuang Guo
Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University
Yitong Zhou
Key Laboratory of Semiconductor Photovoltaic Technology and Energy Materials of Inner Mongolia, Centre for Quantum Physics and Technology Research, School of Physical Science and Technology
Bin Zhou
Pengfei Pang
Joint School of National University of Singapore and Tianjin University International Campus of Tianjin University
Wei Ge
State Key Laboratory of Mesoscience and Engineering
Chang Liu
Hong Shan
Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University
Huanhuan He
Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University