**1. Introduction**

Among the Schwann cells (SCs), non-myelinating Schwann cells (NMSCs) represent an important category that was not extensively studied, although the gathered data demonstrate they are essential for axon maintenance and neuronal survival in the peripheral nervous system (PNS). Extending the knowledge on NMSCs biology could open new perspectives on the normal functioning of PNS as well as for better understanding the mechanisms underlying various pathological conditions and further on for developing new therapeutic approaches in peripheral nerve diseases.

The NMSCs encompass two major cell types, according to their distribution: Schwann cells of Remak fibers and the specialized perisynaptic/terminal Schwann cells at neuromuscular junctions (NMJ). In addition in this category are also included the glial cells found in some sensory transducers, such as the Pacinian and Meissner's corpuscles, as well as in the sensory and autonomic ganglia, where they are called satellite cells [1]. In pathological circumstances like axonal loss or demyelination, the former myelinating Schwann cells also become a class of NMSCs. Conversely, all NMSCs retain the potential to myelinate [2], if they receive the appropriate cues, most of which derive from the associated axons, along with some fate-controlling genes that act cell-autonomously within SCs [3, 4].

#### **Figure 1.**

*Schwann cell lineage. SCs derive from the neural crest cells, after contacting nascent nerves during embryogenesis. Neural crest cells give rise to SC precursors, in early embryonic nerves which further differentiate into immature Schwann cells, in late embryonic and perinatal nerves. Postnatally, iSch will further differentiate either toward myelinating cells or non-myelinating cells according to axon-derived signals. The myelinating cells form the myelin sheath of large axons. The non-myelinating cells ensheath small axons forming unmyelinated fibers, called Remak bundles, or they migrate toward the neuromuscular junctions, covering the axon terminals, where they become terminal/perisynaptic/teloglia Schwann cells.*

#### **Figure 2.**

*Transmission electron microscopy of myelinated (mn, in A) and nonmyelinated (nn, in B) axons of peripheral nerves embedded in the cytoplasm of Schwann cell (Sch). C and D show the Schwann cells and nerve terminals (nt) in neuromuscular junction. (C) The motor end plate formed by folded sarcolemma (junctional folds, arrows) accommodates knob-like terminal buttons of the motor nerve (nt). (D) The myelin sheath (m) covering the axon ends (nt) in the vicinity of neuromuscular junction and Schwann cell extends into the synaptic cleft (arrowheads).*

*Non-Myelinating Schwann Cells in Health and Disease DOI: http://dx.doi.org/10.5772/intechopen.91930*

All Schwann cells derive from multipotent progenitor cells of the neural crest (**Figure 2**). The fate decision mechanism of SCs to become myelinating cells or to form RSCs is not fully understood, although the plasticity of SCs in various studies is recognized. Thus, some studies proved that if myelinated nerve segments are grafted, on a nerve that contains especially unmyelinated fibers, transplanted SCs do not myelinate, and equally, RSCs can produce a myelin sheath when they are grafted onto a myelinated nerve [2, 5].

After contacting nascent nerves during embryogenesis, neural crest cells give rise to SC precursors (SCP), which further differentiate into immature Schwann cells (iSC), in late embryonic and perinatal nerves (**Figure 1**). After birth, iSC will further differentiate either toward myelinating cells or non-myelinating cells according to axon-derived signals. The myelinating SCs form the myelin sheath of large axons (**Figure 2A**). The non-myelinating cells ensheath small axons forming unmyelinated fibers, called Remak bundles (**Figure 2B**), or they migrate toward the neuromuscular junctions, covering the axon terminals, where they become terminal/ perisynaptic/teloglia SCs (**Figure 2C** and **D**).

This chapter addresses the main types of NMSCs, in terms of biological aspects and their role, aiming to highlight their importance for a better understanding of pathological mechanisms underlying various peripheral nervous system diseases.
