Abstract
Neural crest (NC) cells are a multipotent stem cell population that give rise to a diverse array of cell types in the body, including peripheral neurons, Schwann cells (SC), craniofacial cartilage and bone, smooth muscle cells, and melanocytes. NC formation and differentiation into specific lineages takes place in response to a set of highly regulated signaling and transcriptional events within the neural plate border. Premigratory NC cells initially are contained within the dorsal neural tube from which they subsequently emigrate, migrating to often distant sites in the periphery. Following their migration and differentiation, some NC‐like cells persist in adult tissues in a nascent multipotent state, making them potential candidates for autologous cell therapy. This review discusses the gene regulatory network responsible for NC development and maintenance of multipotency. We summarize the genes and signaling pathways that have been implicated in the differentiation of a postmigratory NC into mature myelinating SC. We elaborate on the signals and transcription factors involved in the acquisition of immature SC fate, axonal sorting of unmyelinated neuronal axons, and finally the path toward mature myelinating SC, which envelope axons within myelin sheaths, facilitating electrical signal propagation. The gene regulatory events guiding development of SC in vivo provides insights into means for differentiating NC‐like cells from adult human tissues into functional SC, which have the potential to provide autologous cell sources for the treatment of demyelinating and neurodegenerative disorders.
Highlights
INTRODUCTION TO THE NEURAL CREST CELLSOften referred to as the “fourth germ layer,” the neural crest (NC) is a multipotent and migratory stem cell population that contributes to a wide array of organs and tissues in the vertebrate embryo, including autonomic ganglia, sensory neurons, adrenal and thyroid glands, cartilage and bone of the face, smooth muscle cells of some major arteries, and melanocytes in the skin.[1,2] NC formation is first observed at stage 9 of human embryogenesis and extends till stage 20 as per the Carnegie staging system.[3]
NC cells have attracted great interest due to their ability to differentiate into multiple cell types.[156]
Regardless of source, NC-like cells have been coaxed to differentiate into Schwann cells (SC), neurons, chondrocytes, smooth muscle cells, and even cardiomyocytes,[2,179,180] providing a multipotent stem cell source for the treatment of demyelinating and other neurodegenerative disorders
Summary
Often referred to as the “fourth germ layer,” the neural crest (NC) is a multipotent and migratory stem cell population that contributes to a wide array of organs and tissues in the vertebrate embryo, including autonomic ganglia, sensory neurons, adrenal and thyroid glands, cartilage and bone of the face, smooth muscle cells of some major arteries, and melanocytes in the skin.[1,2] NC formation is first observed at stage 9 of human embryogenesis and extends till stage 20 as per the Carnegie staging system.[3] Neural crest stem cells (NCSC) were first identified in rodents by Stemple and Anderson and isolated using cell sorting for NC-specific cell surface protein p75NTR (neurotrophin receptor [NTR]) These p75NTR+ cells could self-renew and generate. Nagoshi et al used double-transgenic mouse strains P0 and Wnt1-Cre/
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