Direct and Indirect Neurogenesis in the Mammalian Neocortex

ABSTRACT The neocortex is the most complex cellular system in the natural world, the seat of motor, sensory and executive function. While many of the mechanisms responsible for neocortical formation have been discovered, key aspects of how neural precursor cells produce the exceptional variety of cortical neurons are unknown. Recent advances in genomic analysis and in vivo cellular labeling enable study of cortical development at an unprecedented level of resolution. Here we propose to operationalize our ability to label and track specific lineages of neurons, based on whether they were produced directly or indirectly from the apical radial glia stem cells, to determine how lineage information is used to construct the proper circuits in the developing neocortex. These studies will use emerging evidence and new tools to elucidate how neural precursor lineages influence neocortical growth.