Cerebral cortex development: analysis of transcriptional and physiological aspects in humans ​

The cerebral cortex is a complex structure that contains a variety of cells distributed along a six-layered structure, organized in specialized areas. Its formation occurs during embryonic development in a process called neurogenesis. One of the most sophisticated biological structure is originated from a small number of cells: neural stem cells (NSCs). Although this process has been deeply studied, information about the cellular and molecular mechanisms are still lacking. In this thesis were firstly analysed outer radial glial cells (oRGs, derived from NSCs), which are responsible for most of the human cortical formation, defined as primary neural stem cells of the cortex. Trough single-cell mRNA sequencing it was demonstrated their ability to form self-sustained proliferative niche, supporting brain development. Afterwards, another crucial class of cells was taken into consideration: neural intermediate progenitor cells (nIPCs), namely, transit amplifying cells derived from radial glia which can directly generate most neurons of the cortex. An analysis of the spatiotemporal, transcriptional, and morphological diversity of nIPC was performed, identifying different classes. Lastly, a physiological analysis of different cell types present in the developing human cortex was considered, since this characteristic is far from being completely understood. Variation in concentration of Ca2+ was also considered, in order to associate lineages of cells to a specific response to neurotransmitters. All together, these results provide a better understanding of the molecular and cellular mechanisms occurring during human neurogenesis. These findings may be broadly applied to in vitro tools and models for further studies in cortical development, thereby providing insight into the dysregulations at the base of neurodevelopmental disorders.