MEF2C is a transcription factor expressed in neural lineages. After transient transfection, the MEF2 family of factors can act synergistically with the neural-specific transcription factor, MASH-1, and activate exogenous neural-specific promoters. To determine whether MEF2C is capable of modulating endogenous gene expression, P19 cell lines were analyzed that overexpressed MEF2C, termed P19[MEF2C] cells. Here we show that P19[MEF2C] cells differentiate into neurons when aggregated with ME(2)SO. MEF2C-induced neurons expressed neurofilament protein, the nuclear antigen NeuN, as well as MASH-1. Our results indicate that MEF2C can directly or indirectly activate the expression of MASH-1, leading to neurogenesis.