Mechanisms and Roles of Axon-Schwann Cell Interactions

Abstract

Schwann cells (SCs) cover most of the surface of all axons in peripheral nerves. Axons and these glial cells are not only in intimate physical contact but also in constant and dynamic communication, each one influencing and regulating the development, function, and maintenance of the other. In recent years, there has been significant progress in the understanding of the molecular mechanisms of axon-Schwann cell interactions, particularly those relevant for postnatal development and maintenance of nerve function and structure. In this review, we discuss recent progress in four aspects of axon-Schwann cell interactions, including the roles of the neuregulin1 (NRG1)-erbB signaling pathway, the mechanisms underlying the formation and function of the node of Ranvier, the role of perisynaptic Schwann cells at the neuromuscular junction, and the mechanisms that generate Schwann cell tumors.Along the entire length of mammalian peripheral nerves, axons of motor, sensory, and autonomic neurons are in close association with SCs. The intimate contact between SCs and peripheral axons provided a first indication that these cells interact in important ways. In the mature nervous system, Schwann cells can be divided into four classes: myelinating cells (MSCs), nonmyelinating cells (NMSCs), perisynaptic Schwann cells (PSCs) (also known as terminal Schwann cells), and satellite cells of peripheral ganglia. These classes are based on their morphology, biochemical makeup, and the neuronal types (or area of their axons) with which they associate. MSCs, the best characterized SC, wrap around all large-diameter axons, including all motor neurons and some sensory neurons. Each MSC associates with a single axon and creates the myelin sheath necessary for saltatory nerve conduction (Fig. 1 A). NMSCs associate with small-diameter axons of C-fibers emanating from many sensory and all postganglionic sympathetic neurons. Each NMSC wraps around several sensory axons to form a Remak bundle, keeping individual axons separated by thin extensions of the Schwann cell body (Fig. 1 B).

Integrins are necessary for the development and maintenance of the glial layers in theDrosophilaperipheral nerve

“…In the center of Drosophila peripheral nerves, the WG embed axons in bundles or individually within single membrane wraps, similar to the non-myelinating Schwann cells of vertebrate peripheral nerves (Corfas et al, 2004). Our results show that WG predominantly express PS3 and PS integrin subunits in complexes positive for Ilk and Talin along the WG membrane.…”

Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

“…The expression of the GFAP, CD44 (Fig. 1B, F) and NGF-R (data not shown) indicated that this cell line expressed important molecules that are characteristic of non-myelinating SC (Corfas et al 2004). Even though ST88-14 cells presented a non-myelinating phenotype, a low level of MBP was detected in these cells (Fig.…”

Schwann cell targeting via intrasciatic injection of AAV8 as gene therapy strategy for peripheral nerve regeneration

“…Thus, while axonal signals regulate myelin production, myelin, synthetized by Schwann cells, regulates axonal diameter, formation of the nodes of Ranvier and nerve conduction velocity. 1 In this context, overexpression of a therapeutic protein by the appropriate cell type may be crucial to maintain or enhance both, the crosstalk between different cell types and the PNS function.…”