TY - JOUR
T1 - Wnt-Dependent Oligodendroglial-Endothelial Interactions Regulate White Matter Vascularization and Attenuate Injury
AU - Chavali, Manideep
AU - Ulloa-Navas, Maria José
AU - Pérez-Borredá, Pedro
AU - Garcia-Verdugo, Jose Manuel
AU - McQuillen, Patrick S.
AU - Huang, Eric J.
AU - Rowitch, David H.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/12/23
Y1 - 2020/12/23
N2 - 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.
AB - 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.
KW - Wnt signaling
KW - endothelial cells
KW - hypoxic-ischemic encephalopathy
KW - oligodendrocytes
KW - tip cell angiogenesis
KW - white matter
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U2 - 10.1016/j.neuron.2020.09.033
DO - 10.1016/j.neuron.2020.09.033
M3 - Article
C2 - 33086038
AN - SCOPUS:85095439178
SN - 0896-6273
VL - 108
SP - 1130-1145.e5
JO - Neuron
JF - Neuron
IS - 6
ER -