I  Introduction

II In Vitro Systems

III  Control of Schwann Cell Proliferation

IV Myelin-Related Behaviors in Vitro

V  Schwann Cell Influences Directed to Neurons

VI  Conclusions and Projections

References

A Glial Cells in the Peripheral Nervous System

In the peripheral nervous system (PNS), glial cells occur in two categories: (i) the satellite cells that surround the neuronal somata within the ganglionic mass, and (ii) the Schwann cells that surround the axons coursing outside the central nervous system (CNS), whether such axons derive from PNS ganglionic neurons or CNS spinal cord motor ones and whether or not they become myelinated. As shall be pointed out throughout this review, these two subdivisions of peripheral glia are likely to represent the same cell element assuming different morphological, biochemical, and possibly functional properties according to their position relative to the neuron. The term “Schwann cell,” which will be generally used in the review, therefore may well include the satellite subset of peripheral glial cells.

Satellite and Schwann cells spend most of their developmental life in close physical contact with the neuron. This topographical feature has been examined in great detail using histological and ultrastructural techniques and has prompted a firm belief that biochemical and functional interactions must parallel the physical associations. The most conspicuous Schwann-neuron interaction is the generation of myelin around certain axons; formation, maintenance, breakdown, and restoration of myelin have been extensively investigated in vivo. Much less attention, however, has been given to the identification and characterization of other roles that Schwann cells must play. The complex relationship between Schwann cells and the neuronal membrane strongly implies that these other roles are of critical importance to normal PNS function. Glia-neuron interactions in the CNS are equally indicative of similar glial roles (cf. Varon and Somjen, 1979).

Schwann-neuron interactions must be considered to occur in two ways, from neuron to glia and from glia to neuron. Communications in either direction are likely to be mediated by both macrosignals (i.e., macromolecules presented on cell surface membranes or transmitted through the intercellular fluid) and microsignals (ions, neurotransmitter-related molecules, metabolites, etc.). In vivo studies have provided evidence for the occurrence of some such signals. We know that neurites supply Schwann cells with mitogenic and myelinogenic signals, triggering proliferation and myelin-forming processes, respectively (Asbury, 1967; Landan and Hall, 1976; Speidel, 1964; Friede and Samorajski, 1968; Raine, 1977). Certain transmitters, such as γ-amino butyric acid (GABA), have been shown to be avidly taken up by satellite cells (Schon and Kelly, 1974a,b; Bowery et al., 1979a,b), even though the functional meaning of this glial property remains unclear. There is a strong suspicion that Schwann cells provide signals for both growth and guidance of regenerating axons (cf. Varon and Bunge, 1978; Varon and Somjen, 1979). Nevertheless, thus far, in vivo studies have failed to characterize in any detail the signals themselves and/or their immediate responses.

In recent years a new, very powerful tool has been developed, namely the use of neural cell cultures (cf. Varon, 1975b; Fedoroff and Hertz, 1978; Schoffeniels et al., 1978; Giacobini et al., 1980). In vitro studies can strongly complement in vivo ones. Under appropriate culture circumstances, both neurons and glial cells can display the typical features and behaviors for which they are known in vivo, and thus “recapitulate” development or regeneration as they are perceived in situ (Waxman et al., 1977). In addition, they offer opportunities not available to in vivo research, such as (i) purified populations of Schwann cells and neurons, which can be investigated separately from or after controlled recombination with each other, and (ii) living cells that can be examined in an environment that is uniform, controlled, and amenable to experimental modification.

This review will attempt to provide a detailed survey of the in vitro tools that have become available for the investigation of Schwann cells, and of the substantial amount of information already accumulated through their use. As a background to the following sections, the remainder of this first section will summarize main points derived from in vivo studies of normal and pathological situations. For a detailed coverage of in vivo studies, the reader is encouraged to consult some of the several reviews already available on the subject (Bunge, 1970; Webster, 1974; Aguayo et al., 1979; Pannese, 1980; among others).

B Normal Development of Schwann Cells in Vivo