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Cellular and molecular properties of the developing cerebral cortex progenitors in primate

On The September 28, 2015

Julie Waltispurger

Team Director - Colette Dehay

Abstract :

During development, neural progenitors generate all cells that constitute the mammalian brain. During evolution, brain size increased, and this increase is attributed to differences in the quantity and the proliferative/differentiative abilities of neural progenitors. There are two major types of cortical progenitors: apical progenitors (APs) and basal progenitors (BPs) which play an important role in cortical expansion.

In Primates, the organization of the germinal zones is more elaborate than in rodents and is characterized by an expanded subventricular zone (SVZ) that is split into cyto-architecturally distinct compartments: the inner SVZ (ISVZ) and the outer SVZ (OSVZ), which constitutes a primate specific germinal zone. A recent study in our team showed that the primate OSVZ is populated by a mosaic of BPs, comprising four different types of basal Radial Glial cells (bRGs) and intermediate progenitors (IPs). All these types of BPs are able to self-renew and directly generate neurons.

The complexity of the primate brain combined with limited access to biological material make it difficult to study. To overcome this problems, in vitro models of primate corticogenesis have been recently developed from Embryonic Stem cells (ESC)s. These cerebral organoïds contain layers which mimic the developing human cerebral cortex. As in the native brain, in the innermost layer — the equivalent of the VZ — RG cells divide and give birth to neurons. More importantly, these organoïds contain the equivalent of the OSVZ, containing a substantial number of cells bearing specific features of BPs.

The main objective of my thesis is to study the molecular features of the different BP types of the primate OSVZ. In this purpose, I developed an in vitro system for 3D cortical differentiation of monkey ES cells in order to recapitulate in vivo monkey corticogenesis.