The Heterogeneity of Adult Neural Stem Cells and the Emerging Complexity of Their Niche

Abstract

Neural stem cells persist in the adult mammalian brain in a neurogenic niche known as the subventricular zone (SVZ). SVZ neural stem cells (NSCs) can self-renew and are multipotent in culture. In rodents, adult NSCs correspond to SVZ astrocytes (type B cells) that are derived from radial glia, the NSCs of the embryonic and early postnatal brain. Type B cells generate transit-amplifying (type C) cells that give rise to young neurons (type A cells) and oligodendrocytes. Young neurons are born throughout the adult neurogenic niche and migrate tangentially through a complex network of chains that merge into the rostral migratory stream (RMS), a major pathway that leads into the olfactory bulb (OB). Within the OB, young neurons differentiate into multiple types of interneurons. The SVZ was thought to be limited to the lateral wall of the lateral ventricle, but recent work shows that the adult neurogenic niche is significantly more extensive and includes portions of the medial and dorsal walls of the lateral ventricle and the RMS itself. Furthermore, several recent studies explain why young OB neurons are generated in such an extensive region. Type B cells in different regions of the SVZ, although able to self-renew and generate both neurons and glial cells in vitro, are heterogeneous and committed to producing defined neuronal subtypes in vivo. The adult SVZ therefore provides a rich system to study not only neural replacement, but also the cellular and molecular mechanisms underlying regionalization and cell-fate specification.