Transcriptional control of neural crest specification into peripheral glia

Abstract

The neural crest is a transient migratory multipotent cell population that originates from the neural plate border and is formed at the end of gastrulation and during neurulation in vertebrate embryos. These cells give rise to many different cell types of the body such as chondrocytes, smooth muscle cells, endocrine cells, melanocytes, and cells of the peripheral nervous system including different subtypes of neurons and peripheral glia. Acquisition of lineage-specific markers occurs before or during migration and/or at final destination. What are the mechanisms that direct specification of neural crest cells into a specific lineage and how do neural crest cells decide on a specific migration route? Those are fascinating and complex questions that have existed for decades and are still in the research focus of developmental biologists. This review discusses transcriptional events and regulations occurring in neural crest cells and derived lineages, which control specification of peripheral glia, namely Schwann cell precursors that interact with peripheral axons and further differentiate into myelinating or nonmyelinating Schwann cells, satellite cells that remain tightly associated with neuronal cell bodies in sensory and autonomous ganglia, and olfactory ensheathing cells that wrap olfactory axons, both at the periphery in the olfactory mucosa and in the central nervous system in the olfactory bulb. Markers of the different peripheral glia lineages including intermediate multipotent cells such as boundary cap cells, as well as the functions of these specific markers, are also reviewed. Enteric ganglia, another type of peripheral glia, will not be discussed in this review.

Glia in mammalian development and disease

“…All glial cells within the PNS, by contrast, originate from neural crest cells, with gliogenesis starting at E11 in the mouse embryo (reviewed by Jacob, 2015). Analogous to the stepwise specification of CNS neurons and glia from NPCs, neural crest cells first generate sensory neurons of the dorsal root ganglia (DRG) before generating glia.…”

“…By contrast, Schwann cell precursors migrate out of the ganglia into peripheral nerves, where they differentiate into either myelinating Schwann cells or the nonmyelinating Schwann cells that form Remak bundles around small caliber axons. In addition, Schwann cell precursors can also give rise to melanocytes, parasympathetic neurons, endoneurial fibroblasts, or mesenchymal stem cells (Jacob, 2015). Key extrinsic signals that promote the generation of Schwann cell precursors include neuregulin, Notch/Delta and FGFs; by contrast, BMP and Wnt signaling are pro-neural and must be antagonized to allow for gliogenesis.…”

“…Key extrinsic signals that promote the generation of Schwann cell precursors include neuregulin, Notch/Delta and FGFs; by contrast, BMP and Wnt signaling are pro-neural and must be antagonized to allow for gliogenesis. In addition, transcription factors -especially Sox10 and Pax3 -and Hdac1/2 histone deacetylases, which regulate chromatin remodeling, work in concert to promote the formation of Schwann cell precursors from neural crest cells (Jacob, 2015). Neural crest cells also give rise to enteric glial cells in the gastrointestinal tract (Coelho-Aguiar et al, 2015) and olfactory ensheathing cells that reside in both the PNS and the olfactory bulb in the CNS (Barraud et al, 2010).…”

Schwann cells and their transcriptional network: Evolution of key regulators of peripheral myelination

“…Transcriptional regulation of Schwann cell development Each of the steps in Schwann cell development is under control of external stimuli and tightly regulated by transcriptional regulators that form a defined regulatory network (Jacob, 2015;Jessen and Mirsky, 2005;Svaren and Meijer, 2008). Considering that neither Schwann cells nor myelin exist outside the vertebrate subphylum, this regulatory network must be an evolutionary new invention.…”

Kearns-Sayre syndrome with facial and white matter extensive involvement: a (mitochondrial and nuclear gene related?) neurocristopathy?

“…SOX 10, SNAI I, PAX 3, and other connected, namely OCT 6, C-Rett, Endothelin, PAX 6. 48,49 SOX 10 is one of the myelin specific transcription factors expressed in glial cells 50 of CNS and PNS and is important for both myelin development and maintenance. SOX 10 is a NCC development regulator.…”