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Origin and dynamics of oligodendrocytes in the developing brain: Implications for perinatal white matter injury
Authors:Erik van Tilborg  Nienke Wagenaar  Linda S. de Vries  Manon J. Benders  David H. Rowitch  Cora H. Nijboer
Affiliation:1. Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;2. Department of Neonatology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands;3. Department of Pediatrics, Eli and Edythe Broad Center for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, California;4. Department of Paediatrics, Wellcome Trust‐MRC Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
Abstract:
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.
Keywords:brain development  myelination  oligodendrocyte precursor cells  preterm birth  white matter injury
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