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Hif-1α regulates macrophage-endothelial interactions during blood vessel development in zebrafish

Authors: 
Gerri C, Marín-Juez R, Marass M, Marks A, Maischein H-M, Stainier DYR
Citation: 
Nat Comm. 2017;8:15492. doi:10.1038/ncomms15492
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.
Epub: 
Not Epub
Organism or Cell Type: 
zebrafish
Delivery Method: 
microinjection