Definition and Methodologies

Abstract

The study of the induction and regulation of cell differentiation may hold the key to many current health problems, including oncogenesis and neurological diseases. There are two aspects of neural differentiation: (1) induction mechanisms and (2) regulatory mechanisms. The differentiation of nerve cells from presumptive epidermis involves the induction of many differentiated functions unique to nerve cells. The process of induction involves extensive modification of gene expression, i.e., activation and deactiviation of certain genes, as well as precise patterns of growth and organization. Regulatory mechanisms may be important in maximizing the expression of all differentiated functions in the fully mature neuron, and may thereby facilitate the structural organization of the cell. The level of some or all differentiated cellular functions may be regulated by mechanisms distinct in part from those involved in induction. The understanding of both induction and regulatory mechanisms is important. Although there are several experimental models with which to study regulatory mechanisms, none exists for the study of induction mechanisms in mammalian systems. Various cell culture systems undoubtedly provide relatively simple experimental models with which to study certain aspects of neural differentiation that are preferable to the study of intact organisms. However, the cells that compose these systems are already differentiated; therefore, one can only increase or decrease the expression of various differentiated functions through the use of external agents. Using currently available model systems, it has been possible to identify many molecules important in regulating the level of individual differentiated functions in mammalian nerve cells. Using primarily amphibian gastrulas, it has been possible to identify certain molecules that may be involved in inducing neural tissue in ectoblasts. Although genetic control is necessary for the differentiation of nerve cells, other (epigenetic) factors are required for subsequent normal development of neurons. Among these factors, intercellular communications, cellular interactions, and maternal and fetal circulation are the most important during prenatal development of nerve cells. After birth, however, the infant’s own internal and external environments play a vital role in regulating the expression of final stages in nerve cell differentiation. For example, sensory deprivation has catastrophic effects on the development of nerve cells in newborn mammals. The problem of cell differentiation in general and nerve cell differentiation in particular has been discussed in a number of symposia and monographs.1–12