Origin and dynamics of oligodendrocytes in the developing brain: Implications for perinatal white matter injury.

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van Tilborg, Erik 
de Theije, Caroline GM 
van Hal, Maurik 
Wagenaar, Nienke 
de Vries, Linda S 

Infants born prematurely are at high risk to develop white matter injury (WMI), due to exposure to hypoxic and/or inflammatory insults. Such perinatal insults negatively impact the maturation of oligodendrocytes (OLs), thereby causing deficits in myelination. To elucidate the precise pathophysiology underlying perinatal WMI, it is essential to fully understand the cellular mechanisms contributing to healthy/normal white matter development. OLs are responsible for myelination of axons. During brain development, OLs are generally derived from neuroepithelial zones, where neural stem cells committed to the OL lineage differentiate into OL precursor cells (OPCs). OPCs, in turn, develop into premyelinating OLs and finally mature into myelinating OLs. Recent studies revealed that OPCs develop in multiple waves and form potentially heterogeneous populations. Furthermore, it has been shown that myelination is a dynamic and plastic process with an excess of OPCs being generated and then abolished if not integrated into neural circuits. Myelination patterns between rodents and humans show high spatial and temporal similarity. Therefore, experimental studies on OL biology may provide novel insights into the pathophysiology of WMI in the preterm infant and offers new perspectives on potential treatments for these patients.

brain development, myelination, oligodendrocyte precursor cells, preterm birth, white matter injury
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Medical Research Council (MC_PC_12009)
This work was funded by the Wilhelmina Children's Hospital Research Fund and the Brain Foundation Netherlands.