From chance to choice in the generation of neural cell lines

Despite the central importance of cell lines in contemporary studies in cellular and molecular biology, many areas of potential investigation remain impeded by the limited number of lines available and by the difficulty in generating new lines of interest. Thus, there has been a constant pressure to develop improved methods for obtaining cell lines of particular interest. This review examines some of the problems associated with in vitro approaches to cell line generation. In addition, two different ways in which transgenic animals can be used to overcome the limitations of in vitro production of cell lines are discussed. In the first approach, specific promoters are utilized to target expression of immortalizing genes to cells of interest. The second approach is concerned with development of a strain of transgenic animals (the H-2KbtsA58 transgenic mouse) designed to obviate the need for identification of cell-type specific promoters, and in which it is theoretically possible to directly generate conditionally immortal cell lines from any tissue of the body by simple dissection and growth of cells in appropriate tissue culture conditions. Finally, approaches are also discussed in which investigations on the control of precursor differentiation have been applied so as to bypass the need for expression of activated immortalizing oncogenes in the generation of large quantities of conditionally immortalized cells with the capacity to undergo normal differentiation in vitro and in vivo.