| First Author | Zhang S | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 2027 |
| PubMed ID | 32332719 | Mgi Jnum | J:294863 |
| Mgi Id | MGI:6445385 | Doi | 10.1038/s41467-020-15656-4 |
| Citation | Zhang S, et al. (2020) Glial type specific regulation of CNS angiogenesis by HIFalpha-activated different signaling pathways. Nat Commun 11(1):2027 |
| abstractText | The mechanisms by which oligodendroglia modulate CNS angiogenesis remain elusive. Previous in vitro data suggest that oligodendroglia regulate CNS endothelial cell proliferation and blood vessel formation through hypoxia inducible factor alpha (HIFalpha)-activated Wnt (but not VEGF) signaling. Using in vivo genetic models, we show that HIFalpha in oligodendroglia is necessary and sufficient for angiogenesis independent of CNS regions. At the molecular level, HIFalpha stabilization in oligodendroglia does not perturb Wnt signaling but rather activates VEGF. At the functional level, genetically blocking oligodendroglia-derived VEGF but not Wnt significantly decreases oligodendroglial HIFalpha-regulated CNS angiogenesis. Blocking astroglia-derived Wnt signaling reduces astroglial HIFalpha-regulated CNS angiogenesis. Together, our in vivo data demonstrate that oligodendroglial HIFalpha regulates CNS angiogenesis through Wnt-independent and VEGF-dependent signaling. These findings suggest an alternative mechanistic understanding of CNS angiogenesis by postnatal glial cells and unveil a glial cell type-dependent HIFalpha-Wnt axis in regulating CNS vessel formation. |
