Development of the Schwann cell lineage: From the neural crest to the myelinated nerve

Abstract

The myelinating and nonmyelinating Schwann cells in peripheral nerves are derived from the neural crest, which is a transient and multipotent embryonic structure that also generates the other main glial subtypes of the peripheral nervous system (PNS). Schwann cell development occurs through a series of transitional embryonic and postnatal phases, which are tightly regulated by a number of signals. During the early embryonic phases, neural crest cells are specified to give rise to Schwann cell precursors, which represent the first transitional stage in the Schwann cell lineage, and these then generate the immature Schwann cells. At birth, the immature Schwann cells differentiate into either the myelinating or nonmyelinating Schwann cells that populate the mature nerve trunks. In this review, we will discuss the biology of the transitional stages in embryonic and early postnatal Schwann cell development, including the phenotypic differences between them and the recently identified signaling pathways, which control their differentiation and maintenance. In addition, the role and importance of the microenvironment in which glial differentiation takes place will be discussed. V V C 2008 Wiley-Liss, Inc.

P2X7-mediated Increased Intracellular Calcium Causes Functional Derangement in Schwann Cells from Rats with CMT1A Neuropathy

“…Characterization of SC Cultures-The phenotypic characterization of 5-day-old SC cultures from CMT1A and wild type rats revealed expression of PMP22, MPZ, and MBP, which are up-regulated during terminal SC differentiation and myelination (18), together with L1 and GFAP, which should only be expressed by nonmyelinating SC and immature SC precursors (18,19) (Fig. 1).…”

Wnt/Rspondin/β-catenin signals control axonal sorting and lineage progression in Schwann cell development

“…Altered Wnt signaling apparently leads to aberrant differentiation, as shown by the expression of genes characteristic for specific stages of SC development. In spontaneously differentiating SC cultures, activation of Wnt signaling led to an upregulation of markers of the late immature and differentiated SCs, such as Sox2 and GalC (1,40,43), whereas LOF cells failed to up-regulate these genes, indicating a delay of differentiation. To identify directly regulated genes controlled by Wnt signals in SCs, we mapped a cluster of genes significantly down-regulated in β-catenin LOF mutants and up-regulated in cells with activated Wnt signaling.…”

Charcot-Marie-Tooth disease

“…We would not find it surprising that developmental abnormalities in axonal neuropathies could result in shortened internodes if we consider that reciprocal interactions between Schwann cells and axons are critical for the development of myelinated axons. 25,26 Therefore, mutations in both myelin and axon genes may developmentally impede internode formation. It will be interesting to investigate internodal length in skin biopsies with severe, early-onset dysmyelinating CMT to determine whether it is the extent of the shortening of internodes rather than the presence or absence of shortening that best correlates with abnormalities of myelination.…”