Background: Molecular mechanisms underlying reduced expression of Ezh2 during neural differentiation are poorly understood.Results: miR-124 directly down-regulates Ezh2 expression to promote neuronal differentiation.Conclusion: Ezh2 is an important target of miR-124 in the context of neuronal differentiation.Significance: Our report represents a significant advance in understanding the contribution of a microRNA/epigenetic regulatory circuitry to cell fate determination in the neural lineage.