Radial glia give rise to adult neural stem cells in the subventricular zone

TLDR

Neural stem cells resembling astrocytes persist in the subventricular zone and generate many new neurons that migrate to the olfactory bulb, yet their developmental origin remains unknown. The study aims to identify and provide a method to genetically modify the lineage linking neonatal and adult neural stem cells. A lox–Cre-based technique was used to permanently label a restricted population of striatal radial glia in newborn mice. Radial glial cells in neonates give rise to neurons, oligodendrocytes, and astrocytes—including SVZ astrocytes—and their progeny persist into adulthood, producing labeled neuroblasts in the rostral migratory stream at all ages, continuing to generate new neurons in the adult, and forming self‑renewing, multipotent neurospheres, thereby demonstrating that radial glia serve as progenitors early on and give rise to adult SVZ stem cells that sustain neurogenesis throughout life.

Abstract

Neural stem cells with the characteristics of astrocytes persist in the subventricular zone (SVZ) of the juvenile and adult brain. These cells generate large numbers of new neurons that migrate through the rostral migratory stream to the olfactory bulb. The developmental origin of adult neural stem cells is not known. Here, we describe a lox–Cre-based technique to specifically and permanently label a restricted population of striatal radial glia in newborn mice. Within the first few days after labeling, these radial glial cells gave rise to neurons, oligodendrocytes, and astrocytes, including astrocytes in the SVZ. Remarkably, the rostral migratory stream contained labeled migratory neuroblasts at all ages examined, including 150-day-old mice. Labeling dividing cells with the S-phase marker BrdUrd showed that new neurons continue to be produced in the adult by precursors ultimately derived from radial glia. Furthermore, both radial glia in neonates and radial glia-derived cells in the adult lateral ventricular wall generated self-renewing, multipotent neurospheres. These results demonstrate that radial glial cells not only serve as progenitors for many neurons and glial cells soon after birth but also give rise to adult SVZ stem cells that continue to produce neurons throughout adult life. This study identifies and provides a method to genetically modify the lineage that links neonatal and adult neural stem cells.