Successful development of the brain requires the tight regulation of sequential symmetric and asymmetric cell division. The molecular machinery that regulates the mode of cell division during mammalian brain development is poorly understood but now Magdalena Götz and colleagues show that the transcription factor Pax6, a known regulator of neurogenesis and proliferation, regulates both the orientation and mode of cell division in the mouse cerebral cortex (p. 5067). Using live imaging, the researchers show that, in the absence of Pax6, there is an increase in non-vertical cellular cleavage planes in the cerebral cortex. This phenotype, they report, seems to be mediated by the Pax6 target Spag5, which is a microtubule-associated protein. Moreover, long-term live imaging in vitro shows that Pax6-deficient progenitors generate daughter cells with asymmetric fates at higher frequencies than wild-type progenitors. From these and other data, the researchers propose that Pax6 plays a cell-autonomous role in the regulation of cortical progenitor cell division that is independent of apicobasal polarity and cell-cell interactions.