2 Numerology of Neurogenesis: Characterizing the Cell Cycle of Neurostem Cells

Abstract

During development, neurogenesis is a multistep process that includes cell proliferation, cell cycle exit, a choice between survival and death, cell migration, cell differentiation, and cell-fate decisions, including neuron versus glia and neuronal cell class decisions (for review, see Nowakowski et al. 2002). The same multiple steps and associated decisions occur during adult neurogenesis but with several significant differences, the most important being that (1) there are fewer proliferating cells during adult neurogenesis and (2) the selection of neuronal cell classes produced is limited. With respect to the ultimate outcome—the production of functional neurons—each step in this multistep process is, in effect, a possible site of regulation. The complexity of these regulatory steps is described in the other chapters of this book. In this chapter, we deal with the early steps in the process of neurogenesis, i.e., cell proliferation and cell cycle exit. We discuss how the number of cells produced during neurogenesis is regulated by the proliferative capacity of a population of dividing cells. The proliferative capacity, in turn, is determined by the length of the cell cycle, the number of proliferating cells, and the proportion of daughter cells that exit versus reenter the cell cycle. In addition, we review some of the methods for measuring these properties and discuss some of the pitfalls that are commonly encountered. CELL CYCLE CHARACTERIZATION Neurogenesis is driven by cell proliferation, and the core process of cell proliferation is the cell cycle. Conceptually, the cell cycle is simple (Fig. 1A). It...