Distinct sets of precursor cells generate the mammalian cerebral cortex. During neurogenesis most precursors are specified to generate a single cell type and only few are multipotent. The cell-intrinsic molecular determinants of these distinct lineages are not known. Here we describe that retroviral transduction of the transcription factor Emx2 in precursors from the cerebral cortex results in a significant increase of large clones that are generated mostly by symmetric cell divisions and contain multiple cell types, comprising neurons and glial cells. Thus, Emx2 is the first cell-intrinsic determinant able to instruct CNS precursors towards a multipotential fate. To evaluate the role of endogenous Emx2 in cortical precursors, we examined cell division in Emx2-/- mice. These analyses further supported the role of endogenous Emx2 in the regulation of symmetric cell divisions in the developing cortex.