Repository logo

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

Accepted version



Change log


Chavali, Manideep 
Ulloa-Navas, Maria José 
Pérez-Borredá, Pedro 
Garcia-Verdugo, Jose Manuel 
McQuillen, Patrick S 


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 induced increases in OPC numbers, vessel density and endothelial cell expression of the Wnt pathway targets Apcdd1 and Axin2 in white matter, suggesting paracrine OPC-endothelial signaling. Conditional knockout of OPC Wntless resulted in diminished white matter vascular growth in normoxia, whereas 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.



Wnt signaling, endothelial cells, hypoxic-ischemic encephalopathy, oligodendrocytes, tip cell angiogenesis, white matter, Animals, Axin Protein, Cell Differentiation, Endothelial Cells, Endothelium, Vascular, Ferrets, Humans, Hypoxia, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mice, Mice, Transgenic, Oligodendroglia, White Matter, Wnt Signaling Pathway

Journal Title


Conference Name

Journal ISSN


Volume Title



Elsevier BV
European Research Council (789054)
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
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).