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-1alpha transcription factor in this cellular communication. We generated hif-1aa;hif-1ab double mutants in zebrafish, hereafter referred to as hif-1alpha 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-1alpha 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 Tnfalpha-positive, a key feature of classically activated macrophages. Altogether, our data provide genetic evidence that Hif-1alpha regulates interactions between macrophages and endothelial cells starting with the mobilization of macrophages from the AGM.
- Gerri, C.
- Marin-Juez, R.
- Marass, M.
- Marks, A.
- Maischein, H. M.
- Stainier, D. Y. R.
