Mef2c regulates the morphology and synapse formation of cerebellar Purkinje cells

Abstract

Mef2c is an activity-dependent transcription factor that has been shown to play a role during the development of the vascular and nervous systems. However, despite robust expression in neurons of many brain regions, including Purkinje cells in the cerebellum, the function of Mef2c remains poorly understood. In this project, we explore the possible involvement of Mef2c in the development of Purkinje cells in the cerebellum. Using Sholl analysis, we show that Mef2c knockdown in Purkinje cells results in higher number of dendritic intersections while maintaining their soma size compared to Purkinje cells without Mef2c knockdown. Additionally, results from immunohistochemical analysis revealed that Mef2c knockdown results in a reduction in expression/localization of inhibitory (GAD67) and excitatory (vGluT2) synaptic markers on Purkinje cell. Axonal swellings were also observed in the Purkinje cells devoid of Mef2c, suggesting Mef2c knockdown could result in axonal transport impairment and may lead to subsequent neurodegeneration and death. Together, these result indicate that Mef2c plays crucial roles in the development and maintenance of cerebellar Purkinje cells and could serve as a potential target for therapeutic intervention for cerebellum linked neurological disorders.