11 Neurogenic Niches in the Adult Mammalian Brain

Abstract

The mammalian brain is a complex organ composed of trillions of neurons connected with each other in a highly stereotyped yet modifiable manner. Most neurons are born during embryonic development and persist throughout life in the adult brain circuit, in contrast to many other adult tissues, including most from epithelial origins that usually harbor stem cells to maintain homeostatic cellular turnover (Weissman et al. 2001; Li and Xie 2005). The relative stability of neural circuits at the cellular level, especially in higher processing centers of the brain such as the cerebral cortex, was thought to be essential to maintain the ongoing information processing, and any loss or addition to the circuitry component could undermine the cognitive process as a whole (Rakic 1985). Therefore, the discovery of adult neurogenesis—that new neurons are indeed generated in specific regions of adult brains and undergo developmental maturation to become functionally integrated into local neural circuits (Fig. 1a)—came as a surprise (Altman and Das 1965; van Praag et al. 2002). During adult neurogenesis, neural stem cells (NSCs) generate functional neurons through coordinated steps, including cell-fate specification, migration, axonal and dendritic growth, and finally synaptic integration into the adult brain (Fig. 1d). Since the pioneering studies of Altman in the early 1960s (Altman 1962), the process of adult neurogenesis has been unambiguously established in all mammals examined, including humans (Eriksson et al. 1998; Gage 2000; Lie et al. 2004; Abrous et al. 2005; Ming and Song 2005; Lledo et al. 2006; Merkle and Alvarez-Buylla...