12 Adult Neurogenesis: Similarities and Differences in Stem Cell Fate, Proliferation, Migration, and Differentiation in Distinct Forebrain Regions

Abstract

Self-renewal and proliferation of neural stem cells, neuronal fate determination of uncommitted precursors, and migration of neuroblasts are the earliest steps in adult neurogenesis. Self-renewing divisions are required for the maintenance of the stem cell pool, which ensures that neurogenesis continues throughout the lifetime of the organism. Instruction of the stem cell progeny to adopt a neuronal fate is a common feature between the neurogenic niches, yet it is likely that local instructive programs are distinct given that different neuronal phenotypes are generated in neurogenic areas. Finally, immature neurons are born distant from their future location. Thus, migration of the newborn neurons must be tightly regulated to ensure the proper integration of new mature neurons into the neuronal network. In this chapter, we discuss these processes from a functional perspective and summarize current knowledge regarding their cellular and molecular regulation. Stem cells are defined as cells with the potential to generate differentiated progeny and the potential to undergo unlimited self-renewing divisions (Weissman et al. 2001). In the hematopoietic system, the existence of adult stem cells has been proven through assays, in which a single adult cell and its progeny have been repeatedly challenged to reconstitute the entire hematopoietic system in serial transplantations to lethally irradiated organisms (Weissman et al. 2001). The reconstitution of the entire hematopoietic system demonstrates the multipotentiality of the transplanted cell, whereas their ability to do so in serial transplantations indicates the self-renewal of the initially transplanted cell. Such stringent stem cell assays are presently not available...