A cell fate decision map reveals abundant direct neurogenesis in the human developing neocortex

Abstract

The human neocortex has undergone strong evolutionary expansion, largely due to an increased progenitor population, the basal radial glial (bRG) cells. These cells are responsible for the production of a diversity of cell types, but the successive cell fate decisions taken by individual progenitors remains unknown. Here, we developed a semi-automated live/fixed correlative imaging method to generate a map of bRG cell division modes in early fetal tissue and cerebral organoids. Through the analysis of over 1,000 dividing progenitors, we show that bRG cells undergo abundant symmetric amplifying divisions, followed by frequent direct neurogenic divisions, bypassing intermediate progenitors. These direct neurogenic divisions are more abundant in the upper part of the subventricular zone. We furthermore demonstrate asymmetric Notch activation in the self-renewing daughter cells, independently of basal fiber inheritance. Our results reveal a remarkable conservation of fate decisions in cerebral organoids, supporting their value as models of early human neurogenesis.