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

Nature Communications
Claudia GerriDidier Y R Stainier

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.

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Citations

Feb 14, 2018·Current Opinion in Hematology·Ryota L Matsuoka, Didier Y R Stainier
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Datasets Mentioned

BETA
GSE89117

Methods Mentioned

BETA
PCR
confocal microscopy
in vitro transcription

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