Oriented cell divisions induce basal progenitors and regulate neural expansion across tissues and species.

Abstract

Nervous system expansion relies on progenitor proliferation, yet its regional and evolutionary regulation is incompletely understood. While basally dividing progenitors are implicated in neocortical growth, their developmental origins and relevance beyond the cortex remain 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 ectopic emergence 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 signaling. Last, macaque and human retinas display twice as many reoriented divisions as the mouse and naturally contain basal progenitors. These findings show that division orientation is critical for regulating neural progenitor output and scaling tissue growth.