JMY (junction-mediating and regulatory protein) is a vertebrate protein that was originally identified as a P300 cofactor and could augment the transcriptional activity of P53. Recently, JMY was also found to act as an actin nucleator, implying a role of it in central nervous system. However, the expression pattern and biological function of JMY in brain remain largely unclear so far. Here, we found that JMY is selectively enriched in central nervous system and its gene expression is developmentally regulated in mouse brain with a peak of levels at peri-natal stages, suggesting that JMY is involved in the development of cerebral cortex. Combining In Utero electroporation with RNAi technique, we found that down-regulation of JMY expression impaired neuronal migration. The defect of neuronal migration can be rescued by over-expression of JMY. We then generated Jmy-floxed mice and observed consistent results by transfecting CAG-Cre or DCX-Cre vectors with Loxp-Stop-Loxp-eGFP plasmids into Jmy-floxed mouse brains. Thus, the above findings indicate a regulatory role of JMY in neuronal migration during cortical development. Moreover, JMY was also found to affect the activity of neural progenitor cells in VZ/SVZ during embryonic period, as evidenced the results from Jmy^-/-;Nestin-Cre mice and their wild-type control littermates. Taken together, this work underscored the importance of a novel molecular JMY in brain development, providing new insights into the regulatory molecular mechanisms underlying cortical development and the pathogenesis of possible relevant disorders.