Developmental origins of astrocyte diversity in the mouse neocortex
Karine Loulier
ATIP-Avenir “Corticogenesis” Team leader
Institut des Neurosciences de Montpellier – INM

Abstract
To shape an operative brain, neuronal and glial cells must be produced in defined proportions and locations following a strict spatiotemporal regulation. In the mouse neocortex, excitatory pyramidal neurons and astrocytes are produced from cortical progenitors located in the dorsal pallium while cortical interneurons are issued from ganglionic eminences located in the subpallium and oligodendrocytes are generated according to successive subpallial and pallial waves. Neocortical astrocytes constitute an heterogeneous population in terms of morphology, molecular marker expression and function, within and across brain regions in mammals. Despite this multi-level diversity, all neocortical astrocytes were traditionally considered to derive from cortical progenitors located in the dorsal pallium. Using combinatorial genetic markers and multicolor imaging techniques, we previously demonstrated that neocortical astrocytes displayed a plastic development (Clavreul et al. 2019). Exploring the potential contribution of distinct embryonic progenitor domains to the generation of astrocyte subpopulations, we found an additional developmental source for neocortical astrocytes in the form of embryonic progenitors located outside of the dorsal pallium. We also determined that neocortical astrocytes derived from these progenitors spread out in many areas of the postnatal cerebral cortex, but preferentially settle in anterior regions. Performing detailed 3D reconstructions of individualized neocortical astrocyte arborizations, we found that ventrally-derived astrocyte subpopulation displays a simpler morphology but occupies a volume no different from their counterparts issued from the dorsal pallium. Finally, we characterized the molecular signature and properties of these neocortical astrocyte-producing progenitors located outside of the dorsal pallium and we uncovered a complex embryonic domain which contributes to generating neocortical cell diversity. Overall, our results highlight the unsuspected complexity of neocortical astrocyte genesis and open up new avenues to better understand the link between developmental origins, diversity and functions of neocortical cells and their subsequent contribution to the generation of a functioning brain.

Invited by Michel Picardo
Monday June 30th – 11h –  Inmed conference room