Glial origin of mesenchymal stem cells in a tooth model system

Abstract

Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues. The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells. These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives. Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium. It has been thought for decades that the dental mesenchymal stem cells giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue. Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth.

Neuregulin/ErbB Signaling in Developmental Myelin Formation and Nerve Repair

“…They generate immature Schwann cells, endoneurial fibroblasts of fetal nerves as well as melanocytes, parasympathetic neurons and odontoblasts (Joseph et al, 2004;Adameyko et al, 2009;Dyachuk et al, 2014;Espinosa-Medina et al, 2014;Kaukua et al, 2014). Schwann cell progenitors give rise to immature Schwann cells around E16 (Jessen et al, 2015).…”

Integration of tooth morphogenesis and innervation by local tissue interactions, signaling networks, and semaphorin 3A

“…17 Similarly, the glial cells that envelope neurons, are a source of mesenchymal stem cells that can contribute to the repair of injured pulp. 18 Tooth histomorphogenesis and innervation are tightly spatio-temporally integrated During embryogenesis, the development of tissues, organs, and the nervous system, takes place contemporaneously. Given the specific localization of sensory nerve endings in key areas of the mature tooth, and their important functions, it is plausible to assume that the development of tooth-supporting innervation, together with the tooth germ itself, does not occur haphazardly, but is instead strictly choreographed.…”

Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal

“…1A) (Biehs et al, 2013;Juuri et al, 2012;Thesleff and Tummers, 2009). The neurovascular bundle (NVB) provides a niche in which dental mesenchymal stem cells generate pulp cells and odontoblasts (Kaukua et al, 2014;Zhao et al, 2014). The dental epithelial and mesenchymal components produce signaling factors that promote the differentiation and developmental processes of adjacent tissues.…”