Basic principles of neocortex expansion during evolution - a cell biological analysis of neural progenitors in different mammalian species

• Applicant: Professorin Dr. Simone Fietz
• Subject Area: Veterinary Medical Science
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 265041480

Neocortex expansion is a hallmark of mammalian brain evolution. A major cause of this expansion is the increase in the number of neural progenitors and the number of their neurogenic divisions during cortical development. Two principal classes of neural progenitors can be distinguished based on their cell biological and molecular characteristics: the apical progenitors (APs) of the ventricular zone and basal progenitors (BPs) of the subventricular zone (SVZ). A critical feature of the human SVZ is its sub-division into an inner (ISVZ) and outer SVZ (OSVZ) with the latter harboring a new neural progenitor cell type, the basal radial glia cell (bRGC). This cell type maintains features of APs, notably a basal process contacting the basal lamina throughout the cell cycle. This likely enables these cells, in contrast to the majority of mouse BPs, to self-renew. Intriguingly, bRGCs also exist in high abundance in other species including ferret and marmoset, suggesting a more general role of these cells in mammalian corticogenesis. The presence of a separate ISVZ and OSVZ was recently reported for the developing neocortex of cat and sheep. However, if and to what extent bRGCs and other distinct neural progenitor subtypes are present in the developing neocortex of other mammals remains unknown. It is therefore the aim of this project to characterize the molecular and cell biological characteristics of neural progenitors in the developing neocortex of a broad range of mammalian species that exhibit various degrees of cortical expansion including horse, pig, sheep, cow and cat. Using established immunohistochemical markers, this study will investigate the presence and abundance of neural progenitor subtypes during corticogenesis in each species. Moreover, it is planned to determine the cleavage plane orientation of each progenitor subtype division and to characterize the exact cell division lineage from APs to neurons using an in vivo slice culture system and time-lapse imaging. The results will be compared with published data from mouse, ferret, marmoset and human corticogenesis. This will allow to correlate the specific cell biological features of neural progenitors with the degree of cortical expansion, and thus to test the current assumption that a high abundance of self-renewing bRGCs provides a basis for neocortex expansion. Moreover, this approach would establish novel experimental model organisms for the analysis of neural stem cells and human brain disorders.

• DFG Programme: Research Grants