Progression from Extrinsic to Intrinsic Signaling in Cell Fate Specification: A View from the Nervous System

• Published in: Cell 1999-01, Vol.96 (2), p.211-224
• Main Authors: Edlund, Thomas, Jessell, Thomas M
• Format: Article
• Language: English
• Subjects: Animals; Cell Cycle - physiology; Cell Differentiation - physiology; Cell Lineage - physiology; Humans; Intracellular Fluid - physiology; Nervous System - cytology; Nervous System - embryology; Signal Transduction - physiology; Stem Cells - physiology; Transcriptional Activation
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80561-9

The diversity inherent in biological systems has its roots in genetic variation but is revealed through distinctions in the molecular profile and thus the identity of individual cells. The diversification of cell types is evident in an extreme form in vertebrate tissues, and amongst these, the nervous system contains perhaps the richest array of cell types. Even now, the number of distinct neuronal classes that exists is unclear, but traditional estimates of a few hundred mammalian neuronal subtypes appear to be overly conservative. Attempts to understand the mechanisms that generate cell diversity through an analysis of vertebrate neural systems may therefore appear ill advised. Nevertheless, the generation of diverse neural cell types underlies in large part the remarkable information processing capacity of the central nervous system. Thus, one goal of studies of neural cell fate determination not attainable through the use of other tissues is to understand the logic that controls the later assembly of neuronal circuits. Problems posed by the number and complexity of neuronal subtypes may be partly offset by the fact that the mechanisms used to establish neural cell diversity in vertebrates are in many cases conserved with those in other tissues and more primitive organisms. The central issue in the specification of cell fate is the interaction between two general sets of determinative factors: secreted or transmembrane (extrinsic) signals present in a cell's local environment and intrinsic signals that operate in a cell-autonomous manner. Cell identities are assigned through the interplay of both sets of factors, but the relative contribution of each set varies with cell type and developmental time. The task then, is to define how these various environmental, intrinsic, and temporal controls cooperate in establishing the identity of individual cells. Secreted and cell surface proteins control cell fates in a variety of different ways. These strategies are summarized here only briefly, and in this article we instead focus on the issue of how vertebrate neural cells gradually acquire independence from extrinsic signals and become progressively more reliant on intrinsic programs of differentiation. We examine when this transition occurs and the potential mechanisms through which it may be achieved. Neuronal differentiation represents an extreme version of such a transition, since it appears to be accompanied by the loss of potential for reentry into the ce