Heterogeneity and developmental dynamics of mammalian neocortical progenitors

The central nervous system develops from a pool of neural progenitors which, depending on their location and time of division, generate cells committed to differentiate into specific kinds of neurons or glia. In the last decades, the developmental neurobiology field has made important progress in understanding neural cell-type specification: key patterning mechanisms were discovered, the different waves of neurogenesis described, and the dynamics of cortical stratification elucidated. However, only recently, with the advent of single-cell genomics and organoid culturing methods, we were able to measure the transcriptional signatures of individual progenitors systematically and flexibly perturb human development. Together these fine-grained readouts and perturbation possibilities have allowed comparing neural differentiation between species and dissecting the relationship between progenitors' phenotype and fate commitment. This review summarizes recent in vivo and in vitro studies that have contributed to our understanding of temporal progression and coordination of neuronal cell specification across mammals.