In human, genetic predispositions or deleterious environmental conditions may cause adverse effects on the developing brain. In preterm neonates, oligodendrocytes are particularly vulnerable and hypoxic conditions may result in white matter lesions leading to cerebral palsy and long-term disabilities. The glutamatergic transmission plays a critical role in the pathophysiology of these lesions but it is also a key actor involved in developmental mechanisms such as cell differentiation. Previous studies demonstrated a strong expression of the N-methyl-D-aspartate receptor by endothelial cells (eNMDAR) during perinatal life. Whereas it has been shown to regulate the endothelial cell activity, its contribution on neurovascular development remains poorly understood. Because several studies revealed a major contribution of microvessels on the migration of oligodendrocytes, the objective of the study was to investigate the effect of eNMDAR invalidation on i) the differentiation and cortical positioning of oligodendrocytes and, ii) the locomotor activity of the offspring. Using Grin1lox/lox/VeCadcre transgenic mice, immunohistochemical and western blot experiments were conducted at different postnatal stages and showed that CNPase and MBP expression, two markers of mature oligodendrocytes, were markedly decreased in the neocortex of transgenic mice. In contrast, PDGFRa expression, a marker of oligodendrocyte precursors, was increased. Behavioral studies showed that Grin1lox/lox/VeCadcre mice had reduced locomotor activity. Partial recovery of molecular and behavioral defects was found in adults. Altogether, these results suggest that eNMDAR invalidation delayed the differentiation of the oligodendrocyte lineage. They open new research avenues regarding contribution of this receptor in the vessel-associated migration of oligodendrocytes.