The ventricular-subventricular zone (V-SVZ) is a key germinal niche where sustained neural stem cell (NSC) activity is observed throughout postnatal life, supporting the production of both glial cells and GABAergic interneurons. However, NSCs residing in the dorsal-most domain have a pallial origin and rapidly stop producing glutamatergic neurons by entering a state of deep quiescence. The mechanisms driving this rapid decline as well as the capacity of postnatal dorsal NSCs to be reactivated remain to be fully explored.

Here, we expended on previous work to investigate whether modulating Bone Morphogenetic Protein (BMP) signalling can influence NSCs germinal activity in the V-SVZ, at postnatal ages. To this end, we used postnatal electroporation to manipulate Bmpr1a signalling within select V-SVZ microdomains, as well as BrdU labelling and fate mapping approaches. Our results show that BMP pathway inhibition in the dorsal SVZ enhances neurogenesis and oligodendrogenesis, by (re)activating both quiescent and cycling NSCs. Conversely, activation of BMP signalling impairs neuronal migration, maturation and integration, even within the lateral V-SVZ, a region known for sustained NSC activity throughout life.

To further investigate the origin of BMP ligands, we analysed single-cell and spatial transcriptomic datasets covering the V-SVZ and cortex at prenatal and postnatal stages. These analyses identified Cajal-Retzius (CR) cells as potential regulators of dorsal NSC activity. This role was confirmed by histological analyses showing enhanced pallial germinal activity in transgenic mouse models in which CR cells undergo premature death.

Together, our findings provide novel insights on the regulatory mechanisms shaping postnatal NSC germinal activity and suggest novel strategies to modulate neurogenesis after birth.