Junction-mediating and regulatory protein (JMY) is a promoting protein for radial migration of cortical neurons.

Radial neuronal migration is a critical process for the formation of the cerebral cortical layers. Although transcriptional regulators are implicated in neuronal migration, the molecular mechanisms remain incompletely understood. Junction-mediating and regulatory protein (JMY), a p53 coactivator with established roles in embryonic development, has an unclear role in neurodevelopment. Here, we found that JMY is highly expressed in the developing mouse brain, particularly in the ventricular zone and subventricular zone, regions associated with neurogenesis. Knockdown of Jmy resulted in delayed radial migration of cortical neurons, disrupted cell cycle exit, impaired neuronal differentiation, reduced dendritic complexity and produced laminar disorganization. Behavioral tests showed spatial learning and memory deficits in JMY-deficient mice. Proteomic analysis suggested that knocking out Jmy in the mouse brain affects cell cycle-related pathways. Our findings indicate an important role of JMY in neural development and cognitive function in the developing mouse brain, providing novel insights into the molecular mechanisms underlying neuronal migration during corticogenesis.