Date event : December 10, 2021 - 2:00pm Conference / Talk Published on 11/15/2021 - 11:26am
-Nataf Serge, professeur universitaire et praticien hospitalier, Université de Lyon, Examinateur
-Spassky Nathalie, directrice de recherche, Université de Paris, Rapportrice
-Dusart Isabelle, directrice de recherche, Université de Paris, Rapportrice
-Guillemot François, senior group leader, Francis Crick Institute, Londres, Examinateur
-Raineteau Olivier, directeur de recherche, Université de Lyon, Directeur de thèse
The subventricular zone (SVZ) contains neural stem cells (NSCs) in which germinal activity persists following birth to produce glial cells and neurons. Shortly after birth, this neurogenesis becomes exclusively gabaergic, because of the rapid closure of the period of glutamatergic neurogenesis. Mechanisms leading to this decline, as well as the possibility to reactivate glutamatergic neurogenesis following injury, remain to be evaluated.
We performed a single cell transcriptome analysis of postnatal dorsal SVZ to explore mechanisms leading to the closure of the glutamatergic germinal activity. We describe an entry into deep quiescence of pallial NSCs, which correlates with Tgfꞵ signaling pathway activity and Hopx expression. This massive entry into quiescence is accompanied by an abnormal differentiation of glutamatergic progenitors and neuroblasts. Thus, several mechanisms converge to close glutamatergic germinal activity within the postnatal SVZ.
We then used a model of neonatal injury (i.e. chronic hypoxia) to test the competence of these NSCs to participate in tissue regeneration. Histological and transcriptomic analysis indicate a reactivation of dorsal SVZ NSCs, which results in the production of sparse cortical glutamatergic neurons. Their specification and maturation can be encouraged by pharmacological activation of the Wnt/ꞵ-catenin signaling pathway, with no detrimental effects on other cell types, including oligodendrocytes as well as the reservoir and activity of adult NSCs.
Altogether, my work provides novel insights on the dynamic and competence of postnatal SVZ NSCs to produce different types of neurons, in health or following injury.