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Several model systems have been used to understand the cellular and molecular mechanisms of differentiation of mammalian nerve cells. Each model system has unique advantages and disadvantages and is suited for the study of only certain aspects of differentiation. In this book, the techniques of these models and the usefulness and limita- tion of each model system are discussed. An awareness of the use and misuse of each model system is important for a rational interpretation of data and for a reasonable comparison of data obtained from different model systems. With the use of clonal lines of neuronal cells and hybrid neural cells (neural cells x nonneural cells), many new concepts have emerged con- cerning the regulation of differentiated functions, the relationship between the expressions of individual differentiated functions, and the relationship between differentiation and malignancy. Some of these concepts have already proved to be relevant to regulation of differentiation in vivo. These new emerging concepts are discussed extensively in this book. Many new agents (physiological and nonphysiological) which induce or increase the expression of one or more differentiated functions have been identified. These agents will be useful biological tools for further studies of the regulation of differentiation in mamma- lian nerve cells. This book describes the role of each agent in d- vii viii PREFACE ferentiation of nerve cells by focusing on different model systems and provides a rational basis for selecting the particular differentiating agents for specific problems of differentiation processes.