Single-cell analysis of the postnatal dorsal V-SVZ reveals a role for Bmpr1a signaling in silencing pallial germinal activity

Abstract

The ventricular-subventricular zone (V-SVZ) is the largest neurogenic region of the postnatal forebrain, containing neural stem cells (NSCs) that emerge from both the embryonic pallium and subpallium. Despite of this dual origin, glutamatergic neurogenesis declines rapidly after birth, while GABAergic neurogenesis persists throughout life. We performed single-cell RNA sequencing of the postnatal dorsal V-SVZ for unraveling the mechanisms leading to pallial lineage germinal activity silencing. We show that pallial NSCs enter a state of deep quiescence, characterized by high bone morphogenetic protein (BMP) signaling, reduced transcriptional activity and Hopx expression, while in contrast, subpallial NSCs remain primed for activation. Induction of deep quiescence is paralleled by a rapid blockade of glutamatergic neuron production and differentiation. Last, manipulation of Bmpr1a demonstrates its key role in mediating these effects. Together, our results highlight a central role of BMP signaling in synchronizing quiescence induction and blockade of neuronal differentiation to rapidly silence pallial germinal activity after birth.