uPAR Overexpression in the Mouse Brain Stimulates the Migration of Neurons Into the Cortex during Embryogenesis
The regulation of neuronal migration in the cerebral cortex during embryonic development is one of the most important, but underinvestigated processes, which determines the correct formation of neural networks and the development of cognitive functions. Mutations of the urokinase receptor (uPAR) gene in mice lead to spontaneous seizures; polymorphisms of the PLAUR gene encoding uPAR in humans are associated with autism spectrum disorders. We have investigated the effect of uPAR overexpression on the radial migration of neurons in the cerebral cortex during mouse embryogenesis. The number of neurons migrating from the ventricular zone of proliferating progenitors to the outer layers of the cerebral cortex was evaluated. We found that uPAR overexpression significantly stimulates radial neuronal migration to the outer layers of differentiating cortex. These data for the first time show uPAR-dependent regulation of neuronal migration in the embryonic period of the cerebral cortex development. Further study of uPAR role in regulating the migration trajectory of neuronal precursors will advance our understanding of the mechanisms of brain formation in health and disease.