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- Title
Hif-1α regulates macrophage-endothelial interactions during blood vessel development in zebrafish.
- Authors
Gerri, Claudia; Marín-Juez, Rubén; Marass, Michele; Marks, Alora; Maischein, Hans-Martin; Stainier, Didier Y R.
- Abstract
Macrophages are known to interact with endothelial cells during developmental and pathological angiogenesis but the molecular mechanisms modulating these interactions remain unclear. Here, we show a role for the Hif-1α transcription factor in this cellular communication. We generated hif-1aa;hif-1ab double mutants in zebrafish, hereafter referred to as hif-1α mutants, and find that they exhibit impaired macrophage mobilization from the aorta-gonad-mesonephros (AGM) region as well as angiogenic defects and defective vascular repair. Importantly, macrophage ablation is sufficient to recapitulate the vascular phenotypes observed in hif-1α mutants, revealing for the first time a macrophage-dependent angiogenic process during development. Further substantiating our observations of vascular repair, we find that most macrophages closely associated with ruptured blood vessels are Tnfα-positive, a key feature of classically activated macrophages. Altogether, our data provide genetic evidence that Hif-1α regulates interactions between macrophages and endothelial cells starting with the mobilization of macrophages from the AGM.
- Publication
Nature Communications, 2017, Vol 8, Issue 5, p15492
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/ncomms15492