Significance Vascular development in different organs is precisely controlled, yet how this process is orchestrated remains to be elucidated. Previously, we found that dysfunction of DEAD-box RNA helicase 24 (DDX24)… Click to show full abstract
Significance Vascular development in different organs is precisely controlled, yet how this process is orchestrated remains to be elucidated. Previously, we found that dysfunction of DEAD-box RNA helicase 24 (DDX24) causes multiorgan vascular defects. Here, we demonstrate the pivotal role of DDX24 in the regulation of vascular development in the brain and trunk. Ddx24 deficiency in zebrafish results in ectopic vessel sprouting in the trunk but inhibited angiogenesis in the brain. Mechanistically, DDX24 inhibits the VEGF pathway by promoting VEGFR2 mRNA degradation in nonbrain endothelial cells (ECs), while activating GPR124/RECK-mediated Wnt signaling in brain ECs. Spatial transcriptome maps DDX24-mediated crosstalk between ECs and neighboring cells in different locations and times. These findings provide insights into the complex mechanisms underlying vascular development.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2025
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