Coordinated neural progenitor adaptations drive primate neocortical downscaling

Abstract Most primates possess a large, highly folded (gyrencephalic) neocortex, a feature present in the primate common ancestor. In contrast, several New World monkey species display a comparatively small and largely smooth, unfolded (lissencephalic) neocortex. One prominent example is the common marmoset, an increasingly popular model in neuroscience. This phenotype likely reflects an evolutionary reduction from the ancestral primate condition, implying modifications in neurodevelopmental programs. One essential basis for neocortical development is the activity and behavior of neural progenitor cells (NPCs). Here, we identify coordinated adaptations in NPC biology that bias neurodevelopmental trajectories toward neocortical downscaling. By combining marmoset and human cerebral organoids with analyses of fetal marmoset neocortical tissue and previously published histological data, we uncover multiple adaptations in apical and basal progenitors that converge on reduced progenitor capacity, alter early progenitor dynamics, and likely constrain neuronal output, thereby limiting the size and folding of the marmoset neocortex.