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ZFIN ID: ZDB-PUB-170520-2
Hif-1α regulates macrophage-endothelial interactions during blood vessel development in zebrafish
Gerri, C., Marín-Juez, R., Marass, M., Marks, A., Maischein, H.M., Stainier, D.Y.R.
Date: 2017
Source: Nature communications   8: 15492 (Journal)
Registered Authors: Maischein, Hans-Martin, Marín-Juez, Rubén, Stainier, Didier
Keywords: Angiogenesis, Haematopoiesis
Microarrays: GEO:GSE89117
MeSH Terms:
  • Alleles
  • Animals
  • Blood Vessels/embryology*
  • Endothelial Cells/cytology*
  • Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit/genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
  • Macrophages/cytology*
  • Microscopy, Confocal
  • Mutation
  • Neovascularization, Pathologic/genetics*
  • Oligonucleotide Array Sequence Analysis
  • Oxygen/chemistry
  • Phenotype
  • Sample Size
  • Signal Transduction
  • Vascular Endothelial Growth Factor A/metabolism*
  • Zebrafish/embryology
PubMed: 28524872 Full text @ Nat. Commun.
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.