Chapter 2 Neural Stem and Progenitor Cells: Lineage and Cell Fate Determination Stephen N. Sansom, Sabhi Rahman, Uruporn Thammongkol and Frederick J. Livesey INTRODUCTION Neurogenesis, the process by which postmitotic neurons are generated from pools of mitotic progenitor cells, is a highly regulated process in all organisms studied (Edlund and Jessell, 1999; Livesey and Cepko, 2001). Different types of neurons are produced in a temporal sequence that is conserved in different species, and different types of neurons are produced in different parts of the nervous system (Cepko et al., 1996). Discrete phenotypes or identities are as- signed to the postmitotic progeny of neural progenitor cells through a process of cell fate determination. To a significant degree, the fates of those progeny are decided within the mitotic progenitor cell before it divides. Thus, progenitor cells have an integrative function whereby they combine extrinsic information in the form of extracellular signals with information intrinsic to the cell to de- cide the fates of their daughter cells, as will be discussed in more detail below. Given the emergence of findings in recent years illustrating the conserva- tion of mechanisms controlling neural cell fate determination in vertebrate and invertebrate development, it is unlikely that alternative mechanisms are acting in adult neural stem cells. Therefore, an understanding of the cellular and mo- lecular mechanisms involved in this process during development will be of di- rect benefit to efforts to exploit neural stem cells for therapeutic uses. The de- velopmental biology of neural cell fate determination can be broadly divided into a series of processes: the induction or appearance of neurogenic tissue(s), that is tissue containing neural stem and progenitor cells; the division of this tissue into distinct territories or regions that go on to form different components of the adult nervous system; and the ordered production of region-specific neu- rons within each territory. Several striking recent studies have clearly shown that this process can be recapitulated in vitro, generating particular classes of neurons from embryonic stem (ES) cells through a series of discrete steps aimed From: Neural Stem Cells: Development and Transplantation Editor: Jane E. Bottenstein © 2003 Kluwer Academic Publishers, Norwell, MA