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

Abstract Radial migration of neurons is a critical process in the formation of the cerebral cortical layers. Transcriptional regulators are implicated in neuronal migration, while 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 brain, particularly in the ventricular zone and subventricular zone, areas known for neurogenesis. ​Knockdown of Jmy led to delayed radial migration of cortical neurons, disrupted cell cycle exit, and impaired neuronal differentiation. Behavioral studies revealeddeficits in spatial learning and memory in JMY-deficient mice. Proteomicanalysis using Jmy-mutant mice suggested that knocking out JMY in the mouse brain affects cell cycle-related pathways. Our findings indicate an important role of JMY in neurogenesis and cognitive function in the mouse developing brain, providing novel insights into the molecular mechanisms underlying neuronal migration during corticogenesis.