PUBLICATION
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, D.Y.R.
- ID
- ZDB-PUB-170520-2
- Date
- 2017
- Source
- Nature communications 8: 15492 (Journal)
- Registered Authors
- Maischein, Hans-Martin, Marín-Juez, Rubén, Stainier, Didier
- Keywords
- Angiogenesis, Haematopoiesis
- Datasets
- 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.
Citation
Gerri, C., Marín-Juez, R., Marass, M., Marks, A., Maischein, H.M., Stainier, D.Y.R. (2017) Hif-1α regulates macrophage-endothelial interactions during blood vessel development in zebrafish. Nature communications. 8:15492.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping