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The origin and development of glial cells in peripheral nerves

Key Points

  • The Schwann cell precursor (SCP) represents the first step in the process of gliogenesis in growing nerves. In addition to generating Schwann cells, these cells are likely to provide essential trophic support to sensory and motor neurons and are necessary for the structural cohesion of peripheral nerves. They also have the potential to generate neurons and may be the source of the fibroblast population that is found in peripheral nerves.

  • In many ways our ideas about CNS and PNS glial cells have changed along a similar trajectory during recent years. In both cases, novel and unexpected glial functions have been determined and glia are increasingly recognized as sources of signals that are essential for the survival and function of neurons and other cells. Furthermore, the emerging idea that glial cells can act as multipotent progenitors seems to be true not only in the CNS, but also in the PNS, as SCPs, like radial glia, can give rise to unexpected lineages that were previously thought to arise from different sources.

  • Although a large number of molecules have now been implicated in the regulation of Schwann cell development, it is notable that our knowledge about postnatal events greatly exceeds what we know about the control of the embryonic phase of the lineage. Neuregulin 1, in particular the axon-associated type III isoform, has emerged as a signalling molecule of fundamental importance and considerable versatility, as it is likely to carry out different functions at different stages of the lineage. Another key regulator is SOX10, which is required for the gereration of Schwann cell precursors from the neural crest. Understanding the signals that regulate the appearance of glial differentiation in neural crest cells, and defining the role of positive and/or negative inductive signals or default mechanisms in this key event remain challenging areas. Another important step will be the clarification of the molecular regulators of myelination.

Abstract

During the development of peripheral nerves, neural crest cells generate myelinating and non-myelinating glial cells in a process that parallels gliogenesis from the germinal layers of the CNS. Unlike central gliogenesis, neural crest development involves a protracted embryonic phase devoted to the generation of, first, the Schwann cell precursor and then the immature Schwann cell, a cell whose fate as a myelinating or non-myelinating cell has yet to be determined. Embryonic nerves therefore offer a particular opportunity to analyse the early steps of gliogenesis from transient multipotent stem cells, and to understand how this process is integrated with organogenesis of peripheral nerves.

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Figure 1: The Schwann cell lineage.
Figure 2: The appearance of early cells in the Schwann cell lineage.
Figure 3: Some of the factors that have been implicated in the control of early Schwann cell development and myelination
Figure 4: Changes in phenotypic profile as cells progress through the embryonic Schwann cell lineage.
Figure 5: Cell and tissue relationships at key stages of Schwann cell development in rodents.

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Correspondence to Kristjan R. Jessen.

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DATABASES

Entrez Gene

BMP2

BRN2

DHH

Egr2

GFAP

IGF2

LIF

NRG1

OCT6

Pax6

PDGFB

SOX10

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Jessen, K., Mirsky, R. The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci 6, 671–682 (2005). https://doi.org/10.1038/nrn1746

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