During cell division, orientation of the mitotic spindle can influence cell fate by controlling the segregation of cell fate determinants. Here, by inactivating the spindle orientation complex protein LGN, Michel Cayouette and co-workers investigate how spindle orientation influences cell fate in two contexts: the mouse retina and the mouse neocortex (p. 575). Their analysis of Lgn-knockout mice reveals that LGN inactivation causes a decrease in the number of vertical divisions (i.e. those occurring with the spindle perpendicular to the neuroepithelium) carried out by retinal progenitor cells (RPCs). By contrast, when looking at the neocortex, they report that LGN increases the incidence of vertical divisions in cortical progenitors. The researchers further show that LGN and hence vertical spindle division in the retina is required for the terminal asymmetric division of RPCs, whereas LGN in the neocortex acts to maintain planar divisions and the self-renewal of cortical progenitors. In summary, these findings demonstrate that LGN inactivation disrupts spindle orientation in both contexts but leads to very different outcomes with regards to cell fate.