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Wnt-Dependent Oligodendroglial-Endothelial Interactions Regulate White Matter Vascularization and Attenuate Injury.

Authors
  • Chavali, Manideep
  • Ulloa-Navas, Maria José
  • Pérez-Borredá, Pedro
  • Garcia-Verdugo, Jose Manuel
  • McQuillen, Patrick S
  • Huang, Eric J
  • Rowitch, David
Publication Date
Sep 29, 2020
Source
Apollo - University of Cambridge Repository
Keywords
Language
English
License
Green
External links

Abstract

Recent studies have indicated oligodendroglial-vascular crosstalk during brain development, but the underlying mechanisms are incompletely understood. We report that oligodendrocyte precursor cells (OPCs) contact sprouting endothelial tip cells in mouse, ferret and human neonatal white matter. Using transgenic mice, we show that increased or decreased OPC density results in cognate changes in white matter vascular investment. Hypoxia promoted both increased OPC numbers and higher white matter vessel density, OPC WNT7A expression and endothelial cell expression of the Wnt pathway targets Apcdd1 and Axin2, suggesting paracrine OPC-endothelial signaling. Conditional knockout of OPC Wntless resulted in diminished white matter vascular growth in normoxia, while loss of Wnt7a/b function blunted the angiogenic response to hypoxia resulting in severe white matter damage. These findings indicate that OPC-endothelial cell interactions regulate neonatal white matter vascular development in a Wnt-dependent manner and further suggest this mechanism is important in attenuating hypoxic injury. / M.C. acknowledges fellowship awards from the American Heart Association and The Children’s Heart Foundation and funding support from a Career Development Grant awarded by Cerebral Palsy Alliance Research Foundation. J.M.G.V is funded by Red deTerapia Celular (TerCel-RD16/0011/0026) and the Valencian Council for Innovation, Universities Science and Digital Society (PROMETEO/2019/075). M.J.U.N was supported by a McDonald Fellowship from the Multiple Sclerosis International Federation. This work was supported by funding from the National Multiple Sclerosis Foundation (to D.H.R.), the Adelson Medical Research Foundation (D.H.R), the European Research Council (D.H.R.) and the National Institutes of Health, NINDS (1K99NS117804 to M.C; P01- NS083513 to D.H.R., E.J.H and P.S.M).

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