Resumen de Characterization of progenitor cell types and lineages in ferret cerebral cortex and its conservation in mammalian phylogeny
Development of the mammalian cerebral cortex, the cell types involved in this process and their lineage relationships have been studied for years. Cortical neurogenesis is viewed as a linear process where apical radial glial cells (aRGCs) give rise to intermediate progenitors (IPCs), and these in turn give rise to excitatory neurons (ENs). Thanks to advances in animal models and the technology for their study, discoveries in recent years show that this a priori simple process actually involves a greater diversity of neural progenitors and more complex relationships than previosuly thought. But how this process is articulated in gyrencephalic mammals (including humans), where the cerebral cortex undergoes very significant expansion and folding, is unclear. In this PhD Thesis, I have characterized the process of cortical neurogenesis in the gyrencephalic ferret using single-cell RNA sequencing (scRNAseq) and cell lineage tracing technology on isolated germinal layers. We have identified different transcriptomic classes of radial glial cells (RGCs) that populate both the ventricular zone (VZ) and the outer subventricular zone (OSVZ), plus an additional type of RGC thought to exist only in the human cortex. We have found that this progenitor cell diversity establishes parallel lineages that converge onto a single type of immature EN. We have also found that the most immature clusters of ENs are prone to express genes related to human malformations of cortical development, especially in the prospective gyrus. Intriguingly, progenitor cell diversity is more similar between gyrencephalic species (i.e. human, ferret) than with lissencephalic species (i.e. mouse). Finally, we have found that the parallel lineages are conserved in human and ferret, while they seem to have been simplified in mouse. My results contribute significantly to our understanding of the evolution of cerebral cortex folding.
