Stem Cell Property of Postmigratory Cranial Neural Crest Cells and Their Utility in Alveolar Bone Regeneration and Tooth Development

Abstract

The vertebrate neural crest is a multipotent cell population that gives rise to a variety of different cell types. We have discovered that postmigratory cranial neural crest cells (CNCCs) maintain mesenchymal stem cell characteristics and show potential utility for the regeneration of craniofacial structures. We are able to induce the osteogenic differentiation of postmigratory CNCCs, and this differentiation is regulated by bone morphogenetic protein (BMP) and transforming growth factor-b signaling pathways. After transplantation into a host animal, postmigratory CNCCs form bone matrix. CNCC-formed bones are distinct from bones regenerated by bone marrow mesenchymal stem cells. In addition, CNCCs support tooth germ survival via BMP signaling in our CNCC-tooth germ cotransplantation system. Thus, we conclude that postmigratory CNCCs preserve stem cell features, contribute to craniofacial bone formation, and play a fundamental role in supporting tooth organ development. These findings reveal a novel function for postmigratory CNCCs in organ development, and demonstrate the utility of these CNCCs in regenerating craniofacial structures.

SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis

“…Previous studies have demonstrated that the combinatorial activity of the BMP and WNT signaling pathways promotes sensory neuron fate during early neural crest cell development (Kléber et al, 2005). After migration, neural crestderived dental mesenchymal cells still possess the potential to differentiate into dentin-secreting odontoblasts as well as chondrocyte-like and osteoblast-like cells during craniofacial development (Chai et al, 2000;Chung et al, 2009;Yamazaki et al, 2007). Here, we have demonstrated that SMAD4 is indispensable for odontoblast differentiation during tooth development and that loss of Smad4 in the dental mesenchyme results in ectopic osteoblast differentiation and bone formation via WNT pathway upregulation.…”

“…Networks of synergistic and antagonistic signals are likely to regulate the development of neural crest derivatives to produce correct cell numbers at the proper time and location. Neural crest-derived odontogenic mesenchymal cells contain multipotential stem cells and can differentiate into dentinsecreting odontoblasts as well as chondrocyte-like and osteoblastlike cells (Chai et al, 2000;Chung et al, 2009;Yamazaki et al, 2007). However, the crucial cues in the signaling network that regulate dental mesenchymal cell fate remain largely unknown.…”

BMP signaling orchestrates a transcriptional network to control the fate of mesenchymal stem cells in mice

“…During embryonic development, multipotent cells with MSC characteristics have been identified in sites where post-migratory cranial neural crest cells (CNCCs) reside (Chung et al, 2009). Similar to human teeth, mouse molar development includes crown formation followed by root initiation and subsequent root elongation.…”

FGF signaling sustains the odontogenic fate of dental mesenchyme by suppressing β-catenin signaling

“…A variety of craniofacial organs and tissues, such as the Meckel's cartilage, maxillary and mandible bone, trigeminal ganglion and dentin-producing odontoblasts, derive from craniofacial neural crest cells (Chai et al, 2000;Chung et al, 2009). Despite originating from the same progenitor population, craniofacial bone and tooth exhibit distinct developmental, morphological and histological characteristics (Lumsden, 1988;D'Souza et al, 1999;Chai et al, 2000;Zhang et al, 2005;James et al, 2006).…”