A fundamental role for division orientation in progenitor output driving cortical and retinal growth is revealed.
Nervous system expansion depends on progenitor proliferation, but how this is regionally and evolutionarily regulated remains unclear. Basally dividing progenitors are thought to drive neocortical growth, but how they are produced and their relevance beyond the cortex remains unclear. We show here that double inactivation of spindle orientation regulators GPSM2 and SAPCD2 in mice completely reorients progenitor divisions in both the neocortex and retina. This shift increases basal progenitors over sixfold in the neocortex and induces their unexpected appearance in the retina, resulting in extra cell layers and ~30% tissue enlargement. Single-cell RNA-sequencing reveals that the induced basal progenitors in the cortex resemble human outer radial glia, and both cortical and retinal progenitors show altered Hippo signalling. Finally, macaque and human retinas display twice as many reoriented divisions as the mouse and naturally contain basal progenitors. These findings show that division orientation critically scales neural progenitor output and tissue growth.