In the postnatal subventricular zone (SVZ) neural stem cells (NSCs) give rise to transit-amplifying precursors (TAPs) expressing high levels of epidermal growth factor receptor (EGFR) that in turn generate neuroblasts. Both TAPs and neuroblasts express distal-less (DLX)2 homeobox transcription factor but the latter proliferate less. Modulation of its expression in vivo has revealed that DLX2 affects both neurogenesis and proliferation in the postnatal SVZ. However, the mechanisms underlying these effects are not clear. To investigate this issue we have here forced the expression of DLX2 in SVZ isolated NSCs growing in defined in vitro conditions. This analysis revealed that DLX2 affects the proliferation of SVZ precursors by regulating two distinct steps of neural lineage progression. Firstly, it promotes the lineage transition from NSCs to TAPs. Secondly it enhances the proliferative response of neuronal progenitors to EGF. Thus DLX2 and EGFR signalling interact at multiple levels to coordinate proliferation in the postnatal SVZ.